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8th International Congress

The Queen Elizabeth II Conference Centre, London, UK

www.psoriasisg2c.com

Programme & Abstracts 30th November – 2nd December 2017

PSORIASISfrom gene to clinic


Email: [email protected]: www.psoriasisg2c.com

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CO-CHAIRS

Jonathan Barker London, UK Christopher Griffiths Manchester, UK

LOCAL ORGANISING COMMITTEE

David Burden Edinburgh, UKCatherine Smith London, UKRichard Warren Manchester, UK SCIENTIFIC COMMITTEE

Hervé Bachelez Paris, France James Elder Ann Arbor, USAMichel Gilliet Lausanne, Switzerland Lars Iversen Aarhus, DenmarkAlexa Kimball Boston, USA James Krueger New York, USAAlan Menter Dallas, USA Errol Prens Rotterdam, The Netherlands Jörg Prinz Munich, GermanyPeter van de Kerkhof Nijmegen, The Netherlands

ORGANISING SECRETARIAT

Psoriasis from Gene to ClinicConference and Events ServicesBritish Association of Dermatologists4 Fitzroy SquareLondon W1T 5HQ, UK

Tel: +44 (0) 20 7391 6358

Email: [email protected]: www.psoriasisg2c.com

PSORIASIS FROM GENE TO CLINIC

8TH INTERNATIONAL CONGRESSTHE QUEEN ELIZABETH II CONFERENCE CENTRE, LONDON, UK

PROGRAMME & ABSTRACTS BOOK


Email: [email protected]: www.psoriasisg2c.comPSORIASIS

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Welcome 3

Congress Information 4- 5

Thursday Scientific Programme 6 - 7

Friday Scientific Programme 8 - 11

Saturday Scientific Programme 12 - 13

Poster Presentations 14 - 25

Invited & Keynote Lecturers Abstracts 26 - 55

Free Communication Abstracts 56 - 71 Poster Abstracts 72 - 128 Author Index 129 - 133

CONTENTS

WELCOME

The outlook for patients with psoriasis has never been better. New medicines are being introduced into clinical practice that offers the prospect of long-term disease control. These advances are built upon significant insights into the immunopathogenesis of psoriasis and how it potentially relates to other conditions. But there is much more that needs to be done. For example, can immunology and genetics provide insight into the mechanisms underlying different forms of psoriasis? Can these insights translate into more targeted therapy for patients? How close are we to delivering the right treatment for the right patient at the right time?

Building on the success of our previous International Congresses, held every three years over the past 21 years, Psoriasis: from Gene to Clinic is designed to provide a forum for experts from around the world to present and discuss cutting edge issues. Delegates are anticipated to include clinicians, scientists and members of the biotechnology and pharmaceutical industries. The Congress will be entirely plenary allowing attendees to listen to all invited and submitted oral presentations and meet all poster presenters. The programmed sessions will be dedicated to key areas of current scientific and clinical interest ranging from genetics and immune mechanisms to comorbidities and therapeutics. Stratification approaches to both the diagnosis and treatment of psoriasis will feature prominently. The scientific programme will include invited lectures from experts drawn predominantly from outside dermatology. These will include keynote lectures given by two internationally renowned experts: Professor Sir John Savill, London, UK and Dr Leroy Hood, Seattle, USA. Between these presentations there will be free communications chosen from submitted abstracts. Each day will feature sponsored lectures, poster presentations and opportunity for informal discussions.

The high quality of the meeting is reflected in our choice of venue. The Queen Elizabeth II Conference Centre is uniquely situated in the shadow of Big Ben and Westminster Abbey. The welcome reception will take place at the Conference Centre and the Congress Dinner will be held at the magnificent Natural History Museum, a unique, historic venue in the heart of London.

Winter is an excellent time to visit London and we look forward to welcoming you.

Jonathan N W N Barker Christopher E M GriffithsSt John’s Institute of Dermatology The Dermatology CentreKings College London, UK University of Manchester, UK



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NOTES FOR SPEAKERS AND POSTER PRESENTERS

The Speaker Preview Room will be located in the East Long room on the third floor. It is essential to the smooth running of the Congress that all speakers take their presentation to the Speaker Preview Room as soon as possible after their arrival at the Congress Venue but not later than 1 hour before the beginning of their session.

SCIENTIFIC POSTER DISPLAY

The scientific poster display will be situated in the Whittle Room on the third floor. The poster area will be available for presenters to mount their posters from 07:30 on Thursday 30th November. Posters are to be removed by 14:00 on Saturday 2nd December. Presenters of odd numbered posters are asked to be at their poster sites for discussion from 12:45 to 13:45 on Thursday 30th November and those with even numbers between the times of 12:15 to 13:15 on Friday 1st December.

AWARDS FOR BEST POSTER AND BEST ORAL PRESENTATION

Awards will be made to the presenters of the best oral and best poster presentation. The presentation of these awards will be made at the end of the last Congress session on Saturday 2nd December.

WELCOME RECEPTION

THURSDAY 30TH NOVEMBER 17:00 - 19:30

A welcome drinks reception will be held in the Britten Room at The Queen Elizabeth II Conference Centre at the end of the day’s scientific sessions on Thursday 30th November. All registered delegates are invited to attend. We hope this will be a perfect opportunity to relax, catch up with old acquaintances and form new friendships.

CONGRESS DINNER

FRIDAY 1ST DECEMBER 19:30 - 23:00

The Congress Dinner will be held at The Natural History Museum. With its outstanding history, the Natural History Museum is an iconic building in the heart of London. With many galleries, collections, paintings and incredible design it remains an outstanding slice of British history. A splendid three course meal will take place in the magnificent Central Hall, the home of the blue whale skeleton.

Tickets should have been purchased in advance when registering and can be found in your delegate pack.

Dress Code: Business or lounge suit

CONGRESS INFORMATION

Transport for the dinner will depart from and return to the Queen Elizabeth II Conference Centre. Coaches will depart at 19:00.

CERTIFICATES OF ATTENDANCE

Certificates of attendance can be found in your delegate pack.

CLOAKROOM

The Cloakroom is located on the Ground Floor.

CPD CREDITS

Psoriasis: from Gene to Clinic has been approved for 15 credits by the Royal College of Physicians, approval number 115363. All physicians registered for CPD must record their attendance hours in accordance with the guidelines given by the RCP.

LUNCH AND REFRESHMENTS

Lunch and refreshments as indicated in the Programme are included in your registration fee.

PROFESSIONAL & PATIENT ORGANISATIONS

The following professional organisations, patient support groups, charities and psoriasis research programmes will be represented at the Congress:

International Psoriasis CouncilThe Psoriasis AssociationThe Psoriasis and Psoriatic Arthritis Alliance British Skin FoundationBritish Association of Dermatologists Biologic Interventions Register (BADBIR)The International League of Dermatological Societies (ILDS)UK TREND

REGISTRATION

Tel: +44 (0)20 7798 4091

The registration desk will be staffed between the following hours:

Thursday 30th November 07:30 – 17:30Friday 1st December 07:30 – 17:30Saturday 2nd December 08:00 – 13:30



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THURSDAY 30TH NOVEMBER 2017

07:30 Registration opens

10:00 – 10:15 Welcome and Introduction J. Barker (London, UK) C. Griffiths (Manchester, UK)

SCIENTIFIC SESSION 1Chairs: H. Bachelez (France), E. Prens (The Netherlands)

10:15 – 10:25 FC – 1 Psoriasis and risk of malignant lymphoma: a population-based cohort study M. Kamstrup, L. Skov, C. Zachariae, J. Thyssen and A. Egeberg

10:25 – 10:35 FC - 2 Developing a therapeutic range and predicting response to biologics in patients with psoriasis: a multicentre prospective observational cohort study T. Tsakok and the PSORT Consortium 10:35 – 10:45 FC - 3 The differential production of interleukin (IL)-26 vs. IL-17 by T helper 17 cells contributes to the development of different forms of psoriasis A. Fries, J. Di Domizio, O. Demaria and M. Gilliet

10:45 – 11:15 Invited speaker The human skin microbiome and implications for disease B. Andersson (Stockholm, Sweden)

11:15 – 11:45 Coffee break

11:45 – 11:55 FC – 4 Psoriasis-associated late cornified envelope proteins have antibacterial activity H. Niehues, L. Tsoi, D. van der Krieken, P. Jansen, M. Oortveld, D. Rodijk-Olthuis, I. van Vlijmen-Willems, W. Hendriks, R. Helder, J. Bouwstra, R. Mesman, L. van Niftrik, E. van den Bogaard, P. Stuart, R. Nair, J. Elder, P. Zeeuwen and J. Schalkwijk

11:55 – 12:05 FC – 5 Environmental antigens may trigger HLA-C*06:02-mediated autoimmunity in psoriasis Y. Arakawa, A. Arakawa, S. Vural, A. Galinski, S. Vollmer and J. Prinz

12:05 – 12:15 FC – 6 Analysis of psoriasis host-microbiome interactions using a universal transcriptomic approach T. Furnholm, M. Foo, J. Henderson, K. Shedden and A. Johnston

THURSDAY PROGRAMME

12:15 – 12:45 Invited speaker Induction and regulation of Th17 Cells V. Kuchroo (Boston, USA)

12:45 – 13:45 Lunch and poster viewing

SCIENTIFIC SESSION 2Chairs: R. Warren (UK), C. Smith (UK)

13:45 – 13:55 FC – 7 Genetic variation contributes to response to biologics: initial findings of the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium N. Dand on behalf of the PSORT consortium

13:55 – 14:05 FC – 8 Comparative evaluation of cellular and molecular changes associated with response to selective interleukin (IL)-23 blockade vs. dual IL-12/23 blockade in psoriasis skin K. Li, K. Campbell, S. Garcet, C. Brodmerkel and J. Krueger

14:05 – 14:15 FC – 9 Functional immunophenotyping analysis reveals adalimumab-induced impairment of tumour necrosis factor signalling in lymphoid cells in psoriasis R.A. Ejarque on behalf of the PSORT consortium

14:15 – 15:00 Keynote lecture The importance of academic-industrial collaboration to the future of medical research J. Savill (London, UK)

15:00 – 15:45 Tea break

15:45 – 16:15 Lilly Sponsored lecture Targeting IL-17: findings from recent clinical trials A. Blauvelt (Portland, USA) This presentation has been organised and funded by Lilly, Lilly products will be discussed in this session.

16:20 – 16:50 Almirall Sponsored lecture The epidemiology and interrelation of psoriasis and other IL-23 related diseases A. Kimball (Boston, USA)

17:00 – 19:30 Welcome Reception The Queen Elizabeth II Conference Centre



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FRIDAY 1ST DECEMBER 2017

SCIENTIFIC SESSION 3Chairs: J. Elder (USA), M. Gilliet (Switzerland)

08:00 – 08:30 LEO Pharma Sponsored lecture Pro-inflammatory redundancy in the IL-17 pathway - the role of the individual IL-17 cytokine family members in psoriasis J. Krueger (New York, USA)

08:35 – 09:05 Janssen Sponsored lecture IL-23 inhibition as a strategy to treat immune-mediated inflammatory diseases J. Prinz (Munich, Germany) & S. Danese (Milan, Italy)

09:05 – 09:15 FC – 10 The genetic basis for most patients with pustular skin disease remains elusive U. Hüffmeier, S. Löhr, P. Schulz, A. Körber, J.C. Prinz, K. Schäkel, S. Philipp, K. Reich, H. Ständer, A. Jacobi, K. Kingo, S. Koks, S. Gerdes, T. Schill, K.G. Griewank, S. Frey, K. Steinz, S. Uebe, M. Sticherling, H. Sticht, P. Gkogkolou, V. Oji, D. Wilsmann-Theis and R. Mössner 09:15 – 09:25 FC – 11 ADAM17 and TIMP3 are psoriasis-relevant checkpoints controlling T helper 17 programming by inflammatory dermal dendritic cells A. Kunze, A. Rendon, S. Oehrl, G. Murphy, A. Enk and K. Schäkel

09:25 – 09:35 FC – 12 Genotype and phenotype analyses revealed novel susceptibility genes and new clinical classification for psoriasis B.-J. Feng, S. McCarthy, H. Li, K. Praveen, J. Walsh, J. Hawkes, M. Milliken, D. Goldgar, J. Reid, J. Overton, F. Dewey, C. Gonzaga-Jauregui, S. Guthery, K. Callis Duffin and G. Krueger

09:35 – 09:45 FC – 13 Advances in genomic studies of psoriasis in China X. Zhang

09:45 – 10:15 Invited speaker From GWAS to systematic host-microbiome association studies in complex immune-mediated diseases A. Franke (Kiel, Germany)

10:15 – 10:45 Coffee break

FRIDAY PROGRAMME

Chairs: L. Iversen (Denmark), J. Krueger (USA)

10:45 – 10:55 FC – 14 iRhom2: a mechanistic hub in keratinocyte hyperproliferation and psoriasis? M. Brooke, T. Maruthappu, A. Chikh and D. Kelsell

10:55 – 11:05 FC – 15 Identifying chromatin interactions between psoriasis-associated variants and target genes using Capture Hi-C Helen Ray-Jones, A. McGovern, P. Martin, K. Duffus, S. Eyre and R.B. Warren

11:05 – 11:15 FC – 16 The psoriasis-associated Act1(D10N) variant reduces responses to interleukin-17 but enhances T helper 17 responses to polyclonal activation S. Lambert, C. Hambro, A. Johnston, R. Nair and J. Elder

11:15 – 11:25 FC - 17 ERAP1 risk variants in psoriasis vulgaris affect autoantigen presentation A. Arakawa, S. Vollmer, E. Reeves, E. James and J.C. Prinz

11:25 – 11:55 Invited speaker Functional variation in the human genome: lessons from the transcriptome T. Lappalainen (New York, USA) 11:55 – 12:05 FC – 18 Tumour necrosis factor blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis C. Conrad, J. Di Domizio, A. Mylonas, O. Demaria, C. Belkhodja, A. Navarini, A.-K. Lapointe, L. French, M. Vernez and M. Gillliet

12:05 – 12:15 FC – 19 Activation of resident T cells in resolved psoriasis reveals tissue responses that stratify clinical outcome I.G. Sérézal, C. Classon, S. Nylén, N.X. Landén, E. Martini, S. Cheuk and L. Eidsmo 12:15 – 13:15 Lunch and poster viewing



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FRIDAY 1ST DECEMBER 2017 CONTINUED

SCIENTIFIC SESSION 4Chairs: A. Kimball (USA), D. Burden (UK)

13:15 – 13:25 FC – 20 Longitudinal follow-up of arterial structure and function in patients with severe psoriasis treated by anti-interleukin (IL)-12/IL-23 agents compared with tumour necrosis factor inhibitors M. Viguier, H. Khettab, I. Hamdidouche, P. Boutouyrie and H. Bachelez

13:25 – 13:35 FC – 21 Real-world experience with apremilast in patients with psoriasis: interim analysis of 104 patients from the APPRECIATE study E. Kleyn, M. Radtke, C. Bundy, K. Eyerich, M. Ståhle, M. Cordey, V. Koscielny, C.E.M. Griffiths and M. Augustin

13:35 – 13:45 FC - 22 Topical methotrexate gold nanoparticles reduce imiquimod-induced inflammation in mice A. Özcan, D. Bunton, G. Macluskie, M. Duric, J. Barry and A. Kolios

13:45 – 13:55 FC - 23 Efficacy and safety of secukinumab in patients who have failed antitumour necrosis factor-α treatment from the U.K. and Republic of Ireland: results of the SIGNATURE study R.B. Warren, J. Barker, D. Burden, A. Finlay, C. Hatchard, P. Jeffery, R. Williams and C.E.M. Griffiths

13:55 – 14:25 Invited speaker Why biologics fail A. Gils (Leuven, Belgium)

14:25 – 15:10 Tea break

FRIDAY PROGRAMME CONTINUED

SCIENTIFIC SESSION 5Chairs: P. Van de Kerkhof (The Netherlands), H. Bachelez (France) 15:10 – 15:20 FC – 24 The genetic analysis of a large pustular psoriasis resource highlights differential effects for IL36RN and AP1S3 mutations S. Twelves, K. Farkas, S.E. Choon, D. Burden, C.E.M. Griffiths, A. Irvine, E. Tan, M. Szell, Z. Bata-Csorgo, C. Smith, F. Capon and J. Barker

15:20 – 15:30 FC – 25 Transcriptomic profiling of interleukin (IL)-36A, IL-36B and IL-36G cytokine responses in keratinocytes demonstrates a high degree of overlap and dependency on MYD88 and nuclear factor-kB signalling W. Swindell, M. Sarkar, M. Beamer, X. Xing, M. Kahlenberg, N. Ward, J. Voorhees, L. Tsoi, Y. Liang and J. Gudjonsson

15:30 – 16:00 Invited Lecture Biology and pathology of IL-36 J. Towne (San Diego, USA) 16:05 – 16:35 AbbVie Sponsored lecture The evolution of T cell targeted therapy in psoriasis J. Barker (London, UK)

16:40 – 17:10 UCB Pharma Sponsored lecture Re-evaluating the role of IL-17F in immune-mediated chronic inflammation: dual neutralisation of both IL-17A and IL-17F as a novel targeting approach in psoriatic diseases S. Shaw (Slough, UK)

19:30 – 23:00 Congress Dinner The Natural History Museum



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SATURDAY 2ND DECEMBER 2017

SCIENTIFIC SESSION 6Chairs: A. Menter (USA), J. Prinz (Germany)

08:40 – 09:10 Novartis Sponsored lecture Disease modification, from bedside to bench L. Iversen (Aarhus, Denmark) & L. Eidsmo (Stockholm, Sweden)

09:15 – 09:45 Celgene Sponsored lecture The complex management of patients with psoriasis and comorbidities: the role of therapy choice P. Gisondi (Verona, Italy)

09:45 – 09:55 FC – 26 Effectiveness, drug survival and safety of fumaric acid esters for moderate-to-severe psoriasis in routine care: results from the German Psoriasis Registry PsoBest M. Augustin, U. Mrowietz, M.A. Radtke, D. Thaci, K. Ralph, A. Körber and K. Reich

09:55 – 10:05 FC - 27 The lymphatic system plays an important role in the migration of pathogenic T cells towards synovial joints and entheses in psoriasis D. Verhaegh, E. Prens, A.M.C. Mus, P.S. Asmawidjaja, N. Davelaar, A. Hofman, J.-B. Jaquet, J.M.W. Hazes, M.R. Kok, E. Lubberts and R.J. Bisoendial

10:05 – 10:15 FC – 28 Systemic inflammation and evidence of a cardiosplenic axis in patients with psoriasis K.F. Hjuler, L.C. Gormsen, M.H. Vendelbo, A. Egeberg, J. Nielsen and L. Iversen

10:15 – 10:45 Invited Lecture Challenging conventional classification dogma: towards a new clinical taxonomy of psoriasis U. Mrowietz (Kiel, Germany)

10:45 – 11:15 Coffee Break

SATURDAY PROGRAMME

Chairs: J. Barker (UK), C. Griffiths (UK)

11:15 – 11:25 FC – 29 Efficacy and safety of risankizumab, an interleukin-23 inhibitor, in patients with moderate-to-severe chronic plaque psoriasis: 16-week results from the phase III IMMhance trial A. Blauvelt, K.A. Papp, M. Gooderham, R.G. Langley, C. Leonardi, J.-P. Lacour, S. Philipp, S. Tyring, M. Bukhalo, J.J. Wu, J. Bagel, E.H. Frankel, D. Pariser, M. Flack, J. Scherer, Z. Geng, Y. Gu, A. Camez and E.H.Z. Thompson

11:25 – 11:35 FC – 30 Quality of care and use of systemic drugs for psoriasis in the past 12 years: results from a series of nationwide health care studies in Germany M. Radtke, M. Augustin and K. Reich

11:35 – 12:05 Invited Lecture The price and value of biologic drugs J. Scannell (Edinburgh, UK) 12:05 – 12:15 FC – 31 Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a phase II study K. Reich, R. Bissonnette, A. Menter, P. Klekotka, D. Patel, J. Li, J. Tuttle and K. Papp 12:15 – 12:25 FC – 32 Certolizumab pegol for the treatment of patients with moderate-to-severe chronic plaque psoriasis: an overview of three randomized controlled trials A. Blauvelt, K. Reich, M. Lebwohl, D. Burge, C. Arendt, L. Peterson, J. Drew, R. Rolleri and A. Gottlieb 12:25 – 12:35 FC – 33 Switching or restarting of tumour necrosis factor-α inhibitors after interruption under daily-life conditions: efficacy report from the Austrian Psoriasis Registry (PsoRA) P. Wolf, W. Weger, L. Richter, A. Mlynek, P. Sator, W. Saxinger, G. Ratzinger, C. Kölli, C. Painsi, C. Bangert, R. Tatarski, M. Schütz-Bergmayr, P. Ponholzer, F. Trautinger, R. Strohal, R. Müllegger, M. Inzinger, R. Lichem, W. Salmhofer and F. Quehenberger

12:35 – 13:20 Keynote lecture Systems Medicine, Big Data and Scientific Wellness are Transforming Healthcare L. Hood (Seattle, USA) 13:20 Presentation of best oral and best poster prize C. Griffiths (Manchester, UK) J. Barker (London, UK)



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30TH NOVEMBER – 2ND DECEMBER 2017

THE QUEEN ELIZABETH II CONFERENCE CENTRE – WHITTLE ROOM

P – 1 Evaluation of serum uric acid among patients with psoriasis in a developing country S.D. Joshi and L. Limbu

P – 2 A transcriptomic study investigating the pathogenesis of generalized pustular psoriasis M. Catapano, F. Capon, F. Ciccarelli and J. Barker

P – 3 Patient perception and the importance of clear/almost clear skin as a treatment goal in moderate-to-severe plaque psoriasis: results of the ‘Clear about Psoriasis’ worldwide patient survey A. Armstrong, S. Jarvis, W.-H. Boehncke, M. Rajagopalan, P. Fernández-Peñas, R. Romiti, A. Bewley, M. O’Donnell, L. Huneault, E. Dekker, M. Sodha and R.B. Warren

P – 4 Immunogenicity with tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, in a pooled analysis of three randomized controlled trials in patients with chronic plaque psoriasis A. Kimball, A. Blauvelt, K. Reich, Q. Li, F. van Aarle, T. Kerbusch and D. Montgomery

P – 5 Next-generation sequencing identifies epidermal microRNAs deregulated in psoriasis skin A. Srivastava, L. Pasquali, F. Meisgen, M. Stahle, N.X. Landén, A. Pivarcsi and E. Sonkoly

P – 6 Effect of adipose-derived stem cells on an imiquimod-induced psoriasiform mouse model by hypodermic injection J. Deng, C. Lu, L. Han and Y. Huang

P – 7 Impairment of gustatory and olfactory senses in plaque psoriasis P. Rüter, V. Grünthaler, Y. Zopf and M. Sticherling

P – 8 Psoriasis in children: a single-centre analysis F. Heppt, J. Raap and M. Sticherling

P – 9 Interleukin-36γ detection via noninvasive tape stripping reliably diagnoses psoriasis A. Keszegpal, A. Latzko, G. Brown, M. Goodfield, P. Laws, T. Macleod, J. Ainscough, A. Alase, D. Reid, J. Wenzel, P. Helliwell, M. Stacey and M. Wittmann

P – 10 Caffeine in the treatment of atopic dermatitis and psoriasis: a review M. Alashqar1 and N. Goldstein

POSTER PRESENTATIONS

P – 11 Population pharmacokinetic modelling of tildrakizumab (MK-3222), an anti-interleukin-23-p19 monoclonal antibody, in healthy volunteers and patients with psoriasis P. Jauslin, P. Kulkarni, R. Wada, S. VataKuti, A. Hussain, L. Wenning and T. Kerbusch

P - 12 Poster withdrawn.

P – 13 Immune modulation by topical PH-10 aqueous hydrogel (rose Bengal disodium) in psoriasis lesions J.G. Krueger, S. Garcet, J. Fuentes-Duculan, N. Kunjravia, I. Cueto, X. Li, J.M. Singer and E.A. Wachter

P – 14 Favourable safety profile of ixekizumab: results from 11 moderate-to-severe psoriasis and three psoriatic arthritis clinical trials A. Gottlieb, K. Papp, W. Xu, L. Mallbris and N. Agada

P – 15 Poster withdrawn.

P - 16 Cytokine effects of apremilast as a mechanism of efficacy in systemic-naive patients with moderate plaque psoriasis: results from the UNVEIL trial B. Strober, M. Alikhan, B. Lockshin and P. Schafer

P – 17 Patient- and physician-reported outcomes with apremilast for patients with plaque psoriasis during routine dermatology care in Germany: an interim analysis K. Reich, S. Bomas, B. Korge, M. Manasterski, U. Schwichtenberg, H. Mentz, K. Groegel and N. Núnez Gómez

P - 18 Shear wave elastography in patients on high-dose methotrexate: a prospective study D. Kivelevitch, R. Rahimi and A. Menter

P – 19 Do patients with certain human leucocyte antigen expression have a higher risk of developing psoriasis? A. Anandan, K. Radhakrishnan, R. Prasada and V.K. Panicker

P – 20 Utility study to map utilities to the Psoriasis Area and Severity Index and Dermatology Life Quality Index instruments in patients with chronic plaque psoriasis C. Baker, J. Sullivan, P. Davey and J. Wilson

P – 21 Secukinumab shows high and sustained efficacy in nail psoriasis: 2.5-year results from the TRANSFIGURE study K. Reich, P. Arenberger, U. Mrowietz, S. Jazayeri, M. Augustin, A. Parneix, P. Regnault, R. You and J. Frueh



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P - 22 Secukinumab pooled and long-term safety: analysis of 19 psoriasis clinical trials P. van de Kerkhof, K. Reich, C. Leonardi, A. Blauvelt, N. Mehta, T.-F. Tsai, R. You, P. Papanastasiou, M. Milutinovic and C.E.M. Griffiths

P – 23 Lysosomal action in the regulation of inflammatory processes on the example of psoriasis K. Bocheńska, M. Moskot, E. Smolińska, J.J.-Banecka and M. Gabig-Cimińska

P – 24 Secukinumab demonstrates significantly lower immunogenicity potential than ixekizumab in human in vitro assays S. Spindeldreher, B. Maillère, E. Correia, M. Tenon, A. Karle, P. Jarvis and F. Kolbinger

P – 25 Decreased expression of interleukin-27 in moderate-to-severe psoriasis and its anti- inflammatory role in an imiquimod-induced psoriasis-like mouse model W. Chen, Y. Gong, X. Zhang, Y. Tong, X. Wang, C. Fei, H. Xu, Q. Yu, Y. Wang and Y. Shi

P – 26 Secukinumab shows high and sustained efficacy in patients with moderate-to-severe palmoplantar psoriasis: 2.5-year results from the GESTURE study A. Gottlieb, J. Sullivan, A. Kubanov, R. You, P. Regnault and J. Frueh

P - 27 Efficacy and safety of infliximab in the treatment of the Chinese patients with psoriasis J.-Z. Guo, W.-H. Wang and C.-L. Zhang

P – 28 Secukinumab clinical outcomes in a tertiary referral centre O. Jagun, S.T. Cheung, O. Jagun and S.T. Cheung

P – 29 Sustained response to adalimumab over multiple years in patients with plaque psoriasis: analyses from the British Association of Dermatologists Biologic Interventions Register (BADBIR) B. Kirby, J.-F. Maa, T. Festini, B. Calimlim and O.R. Servín

P - 30 Successful treatment of psoriasis with secukinumab after ustekinumab in a patient with multiple sclerosis S. Kaneko, H. Oguro and E. Morita

P – 31 Development of pulmonary sarcoidosis in a patient with psoriasis under treatment with ustekinumab: comorbidity or drug-related ‘paradoxical’ phenomenon? C. Fotiadou, E. Lazaridou, E. Sotiriou and D. Ioannides

POSTER PRESENTATIONS CONTINUED

P – 32 Factors associated with the choice of the first biologic in psoriasis: real-life analysis from the Psobioteq cohort E. Sbidian, C. Giboin, H. Bachelez, C. Paul, M. Beylot-Barry, A. Dupuy, M. Viguier, J.-P. Lacour, J.-L. Schmutz, P. Bravard, E. Mahé, N. Beneton, L. Misery, E. Delaporte, P. Modiano, S. Barbarot, S. Régnier, D. Jullien, M.-A. Richard, P. Joly, F. Tubach and O. Chosidow

P – 33 The Psoriasis Association as a role model for other support groups: how far can (dare) we go? H.H. Oon

P – 34 Paradoxical psoriasis caused by tumour necrosis factor inhibitor therapy: a model system to study the interplay between environmental triggers and genetic susceptibility? T. Maruthappu, A. Connolly, S. Mahil, B. Kirkham, P. DiMeglio and C. Smith

P – 35 The coexistence of generalized pustular psoriasis and pemphigus foliaceus in a woman with Cushing syndrome: a case report A. Kusumawardani, S.E. Ilona, D.A. Mira and Suradi Radiono

P – 36 Retrospective audit on psoriasis, assessment and management: National Institute for Health and Care Excellence guideline CG153 within a dermatology department M. Verma, A. Leong and S. Velangi

P – 37 Role of Thevetia neriifolia in the treatment of psoriasis: clinical case report D. Maryam, S. Souad, O.S. Charifa and S.-B. Rachida

P – 38 Large-scale imputation of killer cell immunoglobulin-like receptor copy number in psoriatic arthritis R. Ahn, D. Vukcevic, A. Motyer, D. Ellinghaus, L.C. Tsoi, R.P. Nair, C. Palmer, J. Oksenberg, J. Foerster, J.T. Elder, A. Franke, S. Leslie and W. Liao

P - 39 Psoriasis following PD-1 inhibitor therapy: features and treatment P. O’Connor and J.P. Dutz

P – 40 Evaluation of body composition in patients with psoriasis treated with ustekinumab M. Galluzzo, S. D’Adamio, R. Pastorino, L. Bianchi and M. Talamonti

P – 41 Characteristics and risk profile of patients with psoriasis included in the Turkish national registry PSR-TR N. Onsun, E.B. Baskan, D. Dizman, D.B. Ozkaya, A.C. Erkılıc, G. Ozarmagan and M.A. Gurer

P – 42 Treatment profile of patients with moderate-to-severe psoriasis included in the Turkish national registry PSR-TR N. Onsun, E.B. Baskan, D. Dizman, D.B. Ozkaya, A.C. Erkılıc, G. Ozarmagan and M.A. Gürer



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P - 43 An ongoing independent study to monitor the uptake of interleukin-17 inhibitors among U.S. dermatologists J. Robinson and L. Price

P – 44 Electronic monitoring of psoriasis outcomes and goals in practice: development and introduction of a standard dataset and a digital management system M. Augustin, J. Wimmer, M. Otten, V. Djamei, A. Navarini and M.A. Radtke

P – 45 Real-world data identify reasons for biological switching in patients with psoriasis J. Robinson and L. Price

P – 46 Comanagement with rheumatologists for patients with psoriatic arthritis receiving treatment with a biological agent or apremilast J. Robinson and L. Price

P – 47 Investigation of the role of IKKε role in the pathogenesis of psoriasis I. Weimar, L. Iversen and C. Johansen

P – 48 The interleukin-17A/F heterodimer regulates psoriasis-associated genes through IκBζ T. Bertelsen, C. Johansen and L. Iversen

P – 49 The psoriasis-associated interleukin-17A induces and cooperates with interleukin-36 cytokines to control keratinocyte differentiation and function C. Pfaff, Y. Marquardt, D. Kluwig, K. Fietkau, B. Lüscher and J. Baron

P – 50 Investigation of the efficacy and safety of acitretin treatment in children with pustular psoriasis X. Zhang, J. Liang and C. Li

P – 51 Real-world use of fumaric acid esters in psoriasis: results from the British Association of Dermatologists Biologic Interventions Register (BADBIR) K.J. Mason, M. Lunt, H.J. Hunter, Z.K. Jabbar-Lopez, B. Kirby, C.E. Kleyn, S. Kreppel, K. McElhone, N.J. Reynolds, R.B. Warren and C.E.M. Griffiths; on behalf of the BADBIR Study Group

P – 52 A real-world comparison of effectiveness and safety outcomes between clinical trial-eligible and -ineligible patients in the British Association of Dermatologists Biologic Interventions Register (BADBIR) K.J. Mason, J.N.W.N. Barker, C.H. Smith, P.J. Hampton, M. Lunt, K. McElhone, R.B. Warren, Z.Z.N. Yiu, C.E.M. Griffiths and A.D. Burden; on behalf of the BADBIR Study Group


P – 53 Guselkumab treatment provided higher frequency of complete skin clearance compared with adalimumab treatment among patients with moderate-to-severe plaque psoriasis P. Foley, M. Song, Y.-K. Shen, Y. You, Y. Wasfi and C.E.M. Griffiths

P - 54 Antibodies to guselkumab are not associated with reduction in clinical response or development of injection-site reactions in patients with moderate-to-severe plaque psoriasis Y. Zhu, J.C. Marini, Y. Wasfi, B. Randazzo, Y.-K. Shen, S. Li and H. Zhou

P – 55 Psoriasis Longitudinal Assessment and Registry (PSOLAR): description of demographic data from the Greek population upon full enrolment V. Chasapi, C. Antoniou, D. Rigopoulos, A. Roussaki-Schulze, D. Ioannides, I. Bassukas, W. Langholff and E. Soura

P – 56 Short-term reasons for withdrawal, and safety of apremilast as a monotherapy and combination therapy for psoriasis in clinical practice compared with clinical trials: a multicentre retrospective study A. Ighani, J.R. Georgakopoulos, N.H. Shear, S. Walsh and J. Yeung

P – 57 A comparison of apremilast monotherapy and combination therapy for plaque psoriasis in clinical practice: a multicentre retrospective study A. Ighani, J.R. Georgakopoulos, S. Walsh, N.H. Shear and J. Yeung

P – 58 An evaluation of the quality of life, treatments and resources available for patients with psoriasis in Canada: a comparison of biologic and nonbiologic users A. Ighani and M.F. Manolson

P – 59 Identification of promising biomarkers to predict therapeutic response to biologics in psoriasis A. Medeiros, L. Grine, M. Van Gele, P. Spuls and J. Lambert

P – 60 Evaluation of carcinogenic risk of psoralen,ultraviolet A (PUVA) vs. retinoid,PUVA in patients with psoriasis H. Mashaly, M. Fathy, S. Hamdy and O. Shaker

P – 61 Successful treatment of recalcitrant hyperkeratotic palmoplantar psoriasis with itolizumab: a case series of three patients U. Chakravadhanula and B.K. Jha

P – 62 Systemic therapy and the risk of nonmelanoma skin cancer among patients in the Psoriasis Longitudinal Assessment and Registry R. DeShazo, R. Soltani-Arabshahi, S. Krishnasamy, C. Galindo, W. Langholff, R. Langley, S. Kalia, S. Fakharzadeh, K. Goyal, M. Ståhle, B. Srivastava and G.G. Krueger



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P – 63 Interleukin-10 regulates skin thickness and scaling in imiquimod-induced psoriasis-like skin inflammation in mice X. Xu, E. Prens, E. Florencia, L. Boon, P. Asmawidjaja, A.-M. Otten-Mus and E. Lubberts

P – 64 The identification of interleukin (IL)-17A+, IL-17RA+ and IL-17RC+ lymphoid and myeloid cells in blood of treatment-naive early patients and in synovial fluid of established patients with psoriatic arthritis X. Xu, N. Davelaar, A.-M. Otten-Mus, P. Asmawidjaja, H. den Braanker, J. Hazes, R. Bisoendial, M. Vis and E. Lubberts

P – 65 Distinct and overlapping activities of interleukin (IL)-17A and tumour necrosis factor (TNF) on the expression of proinflammatory cytokines and matric metalloproteinases in psoriatic arthritis: rationale for anti-IL-17A/anti-TNF-α combination therapy? X. Xu, N. Davelaar, A.-M. Otten-Mus, P. Asmawidjaja, J. Hazes, D. Baeten, M. Vis, R. Bisoendial and E. Lubberts

P – 66 Unopposed interleukin (IL)-36 activity promotes clonal CD4+ T-cell responses with IL-17A production in generalized pustular psoriasis A. Arakawa, S. Vollmer, P. Besgen, B. Summer, P. Thomas, T. Ruzicka and J.C. Prinz

P – 67 Remarkable response of recalcitrant hyperkeratotic palmoplantar psoriasis to itolizumab: a case report U. Chakravadhanula and B.K. Jha

P – 68 Effects of methotrexate on treatment and serum inflammatory cytokines in paediatric patients with severe plaque psoriasis Z. Xu, Y. Gu and Z. Wang

P – 69 Sustained remission in a patient with chronic plaque psoriasis treated with itolizumab: a 4-year follow-up experience S.G. Parasramani, G.G. Kunder, S.H. Suresh and D.R. Pawar

P – 70 Treat to target in psoriasis: a Belgian attempt to define a tight control strategy for psoriasis management L. Grine, S. Segaert, J. Lambert, M. de la Brassinne, P.-D. Ghislain, F. Willaert, T. Hillary and J. Lambert

P – 71 Retrospective review of psoriasis ustekinumab outcomes using real clinic data analysed using starting Psoriasis Area and Severity Index (PASI) and worst PASI in the preceding 5 years with PASI 75 and 90 reported C. Goodhead and P. Hampton


P – 72 Role of keratin 24 in human epidermal keratinocytes M. Min, X.-B. Chen, P. Wang, L. Landeck, J.-Q. Chen, W. Li, S. Cai, M. Zheng and X.-Y. Man

P – 73 Deletion of PCSK9 can suppress psoriasis-like inflammation in an animal model M. Chen, R. Yuan, C. Luan, X. Chen, J.M. Osland, S.J. Gerber, M. Dodds and Y. Hu

P – 74 Correlation between Dermatology Life Quality Index and Psoriasis Area and Severity Index in patients with psoriasis treated with ustekinumab J.H. Hesselvig, A. Egeberg, N.D. Loft, C. Zachariae, K. Kofoed and L. Skov

P – 75 Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis A. Egeberg, M.B. Ottosen, R. Gniadecki, S. Broesby-Olsen, T. Dam, L.E. Bryld, M.K. Rasmussen and L. Skov

P – 76 Predictive factors of pruritus among patients with psoriasis C. Ebongo, S. Mansouri and B. Hassam

P – 77 Education of patients with psoriasis C. Ebongo, S. Mai, M. Meziane and B. Hassam

P – 78 Psychiatric comorbidity, psychotropic medication prescribing and suicidality in patients with psoriasis: a population-based cohort study R. Parisi, R.T. Webb, C.E. Kleyn, M.J. Carr, N. Kapur, C.E.M. Griffiths and D.M. Ashcroft

P - 79 Dithranol in psoriasis: keratinocyte–neutrophil cross-talk as the early target T.H. Benezeder, C. Painsi, G. Mayer, U. Schmidbauer, K. Hammer, B. Lange-Asschenfeld and P. Wolf

P - 80 Effectiveness and safety of off-label secukinumab dosing regimens for the treatment of moderate-to-severe plaque psoriasis in adult patients: a retrospective multicentre study M. Phung, J.R. Georgakopoulos, A. Ighani and J. Yeung

P – 81 Comorbidities in patients with psoriasis according to Charlson Comorbidity Index: 6 years of experience in Bogotá, Colombia C. Cortes, E. Peñaranda, D. Chaparro, L. Peña and E. Roa

P – 82 Relationship between age of onset, male-to-female ratio and family history of Japanese patients with psoriasis: comparison with other East Asian countries B. Bayaraa and S. Imafuku



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P – 83 The journey of adult patients with psoriasis towards biologics past and present: results from the BioCAPTURE registry J. van den Reek, M. Seyger, P. van Lüimig, R. Driessen, L. Schalkwijk, M. Berends, P. van de Kerkhof and E. de Jong

P – 84 Skin mast cells: critical drivers of psoriasis? M.J. Barron, C.E.M. Griffiths and S. Bulfone-Paus

P - 85 Secukinumab demonstrates high sustained efficacy and a favourable safety profile through 5 years of treatment in moderate-to-severe psoriasis R. Bissonnette, T. Luger, D. Thaçi, D. Toth, A. Lacombe, S. Xia, R. Mazur, P. Manmath, C. Pascal, M. Milutinovic and C. Leonardi

P – 86 Infliximab is associated with an increased risk of serious infection in patients with psoriasis: results from the British Association of Dermatologists Biologic Interventions Register (BADBIR) Z. Yiu, C. Smith, D. Ashcroft, M. Lunt, S. Walton, R. Murphy, N. Reynolds, A. Ormerod, C.E.M. Griffiths and R.B. Warren

P- 87 Efficacy and tolerance assessment of an anti-itching spray in patients with psoriasis S. Virassamynaik, B. Chadoutaud, C. Eydieux, J. Riviere and M. Sayag

P – 88 Gene expression and protein changes from blood and skin correlate with disease improvement in patients with psoriasis treated with PF06700841, a tyrosine kinase2/ Janus kinase 1 inhibitor L. Xi, E. Kieras, M. Suarez-Farinas, B. Zhang, K. Page, J. Lee, S. Du, L. Fitz, W. Gordon, W. Zhang, J. Krueger and E. Peeva

P - 89 Interleukin (IL)-36γ induces IL-23 production and angiogenesis in psoriasis C. Bridgewood, G. Fearnley, A. Keszegpal, P. Laws, S. Ponnambalam, A. Graham, M. Stacey and M. Wittmann

P – 90 One-year pilot study to evaluate sequential therapy with ciclosporin and itolizumab in treatment of chronic plaque psoriasis U. Chakravadhanula, B.S. Chandrashekar, M. Parekh, D.S. Krupashankar, H.S. Swaroop and D. Pawar

P - 91 Examining the impact of treatment by a dermatologist vs. nondermatologist in psoriasis care M. Porter, N. Golbari, S. Lockwood and A. Kimball


P – 92 Ixekizumab maintains reductions in Psoriasis Area and Severity Index through the third year of treatment: results from the UNCOVER-3 extension study P. Fernández-Peñas, O. Goldblum, L. Berggren, N. Burkhardt and L. Puig

P – 93 Starting biologic treatment sequences for plaque psoriasis with ustekinumab or adalimumab is the most cost-effective: a costutility analysis based on 10 years of Dutch real-world evidence from BioCAPTURE S. Klijn, J. van den Reek, G. van de Wetering, A. van der Kolk, E. de Jong and W. Kievit

P – 94 52-Week results from IXORA-S: a randomized head-to-head trial of ixekizumab and ustekinumab in patients with moderate-to-severe plaque psoriasis C. Paul, P. van de Kerkhof, Y. Dutronc, C. Henneges, M. Dossenbach, K. Hollister and K. Reich

P – 95 The genotype of susceptibility genes in psoriasis predicting the response and hepatotoxicity to methotrexate treatment J. Xu, X. Zhang and K. Yan

P – 96 Evaluation of the efficacy of granulocyte and monocyte adsorption apheresis on skin manifestation and joint symptoms of patients with pustulotic arthro-osteitis H. Kawakami, N. Abe, Y. Matsumoto, H. Hirano, R. Tsuboi and Y. Okubo

P – 97 Multicomponent biomarkers: a novel method for accurate diagnosis of psoriasis F. Lättekivi, E. Reimann, M. Keermann, K. Abram, S. Kõks, K. Kingo and A. Fazeli

P – 98 Genome-wide DNA methylation profiling identifies differential methylation in uninvolved psoriatic epidermis D. Verma, A.-K. Ekman, C.B. Eding and C. Enerbäck

P – 99 Gene expression changes induced by individual interleukin (IL)-17 family cytokines signalling through IL-17RA D.A. Ewald, P. Lovato, T. Skak-Nielsen and H. Norsgaard

P – 100 Validity of self-reported psoriasis in a Danish birth cohort C. Blegvad, T.E.T. Nielsen, C. Zachariae, A.-M.N. Andersen and L. Skov

P – 101 Intentional and unintentional medication nonadherence in psoriasis: the role of patients’ medication beliefs and habit strength R. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft and L. Cordingley; on behalf of the PSORT study group and BADBIR



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P – 102 Prognostic effect of psoriasis and psoriatic arthritis in patients with suspected coronary artery disease assessed by cardiac computed tomography: a multicentre cohort study K.F. Hjuler, S. Winther, M. Bøttcher and L. Iversen

P – 103 Safety of guselkumab in patients with plaque psoriasis through 2 years: a pooled analysis from VOYAGE 1 and VOYAGE 2 K. Reich, K. Papp, A.W. Armstrong, Y. Wasfi, G. Jiang, Y.-K. Shen, B. Randazzo, M. Song and A.B. Kimball

P – 104 Additional efficacy benefit of continuous ixekizumab every-2-week dosing among patients with psoriasis who do not respond by week 12 K. Papp, M. Gooderham, P. Polzer, L. Zhang and M. Augustin

P – 105 Absolute Psoriasis Area and Severity Index improvement through 2 years of guselkumab treatment in the VOYAGE 1 trial of patients with plaque psoriasis K. Papp, C.E.M. Griffiths, A.B. Kimball, S. Li, Y.-K. Shen, Y. Wasfi and A. Blauvelt

P – 106 Guselkumab treatment results in more effective and durable inhibition of T helper (Th)17 and Th22 cells and downstream effectors compared with adalimumab X. Liu, P.J. Branigan, Y. Chen, S. DePrimo, K. Campbell and E.J. Munoz

P – 107 Cost of topical therapies for patients with psoriasis in Georgia K. Tsagareishvili and N. Chijavadze

P – 108 Looking beyond 12 weeks: long-term drug survival and safety of secukinumab in real-world patients with plaque psoriasis J.R. Georgakopoulos, A. Ighani, M. Phung and J. Yeung

P – 109 Efficacy and safety of ixekizumab in secukinumab nonresponders: therapeutic options for nonanti-interleukin-17A-naive patients J.R. Georgakopoulos, M. Phung, A. Ighani and J. Yeung

P – 110 Long-term, real-world efficacy of infliximab for psoriasis L. Mercieca, R.B. Warren and C.E.M. Griffiths

P – 111 Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis in a Chinese population X. Fan, H. Wang, L. Sun, X. Yin, X. Zuo, Q. Peng, K. A. Standish, X. Zheng, Z. Wang, F. Xiao, S. Yang, X. Zhang and N.J. Schork

P – 112 Retrospective study of childhood psoriasis M.S. Zorko and O. Tockova


P – 113 Immature progenitor cells are enriched in psoriasis epidermis A.-K. Ekman, C.B. Eding, I. Rundquist and C. Enerbäck

P – 114 PRINS long noncoding RNA regulates the expression of interleukin-6 and CCL-5 by direct interaction J. Danis, A. Göblös, L. Janovák, Z. Bata-Csörgő, L. Kemény and M. Széll

P – 115 CARD14 variants in pityriasis rubra pilaris A. Göblös, J. Danis, B. Gál, K. Farkas, E. Varga, I. Korom, L. Kemény, N. Nagy, M. Széll and Z. Bata-Csörgő

P – 116 Early changes in peripheral leucocyte populations during oral dimethylfumarate treatment P. Morrison, D. Stölzl, S. Kurras, S. Gerdes and U. Mrowietz

P – 117 Randomized controlled trial of patient-initiated care for patients with psoriasis L. Khoury, T. Møller, C. Zachariae and L. Skov

P – 118 Establishment of an intradermal ear injection model of interleukin (IL)-17A and IL-36γ as a tool to investigate the psoriatic cytokine D. Kluwig, S. Huth, C. Pfaff, L. Huth, Y. Marquardt, K. Fietkau, J.M. Baron and B. Lüscher

P – 119 Pharmacogenomic signature of response to genistein therapy for psoriasis: effects of genistein in vitro and in vivo and its mechanism of action E. Smolińska, M. Moskot, K. Bocheńska, A. Lewczuk, T. Brodniewicz, J. Jakóbkiewicz-Banecka and M. Gabig-Cimińska

P - 120 Itch and pain perception and epidemiology in patients with psoriasis: results from a prospective two-centre study N. Max, K. Torz, U. Mrowietz, V. Oji, S. Ständer and S. Gerdes

P – 121 Body locations of difficult-to-treat psoriasis in the era of treatment with biological agents: a Danish multicentre study K.F. Hjuler, L. Iversen, K. Kofoed, M. Rasmussen, L. Skov and C. Zachariae

P – 122 The effect of monomethylfumarate on human blood neutrophils I. Suhrkamp, A.-S. Erkens, P. Morrison and U. Mrowietz

P – 123 Psychological distress in patients using systemic therapies for psoriasis: the role of beliefs about illness and anger suppression R. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft and L. Cordingley; on behalf of the PSORT study group and BADBIR



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29

INDUCTION AND REGULATION OF TH17 CELLS

PROFESSOR VIJAY KUCHROOBoston, USA

Dr. Vijay Kuchroo is the Samuel L. Wasserstrom Professor of Neurology at Harvard Medical School, Senior Scientist at Brigham and Women’s Hospital, and Co-Director of the Center for Infection and Immunity, Brigham Research Institutes, Boston. Vijay Kuchroo is also an associate member of the Broad Institute and a participant in a Klarman Cell Observatory project that focuses on T cell differentiation. He was just named the Director of the newly formed Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital. His major research interests include autoimmune diseases - particularly the role of co-stimulation - the genetic basis of experimental autoimmune encephalomyelitis and multiple sclerosis, and cell surface molecules and regulatory factors that regulate induction of T cell tolerance and dysfunction. His laboratory has made several transgenic mice that serve as animal models for human multiple sclerosis. Dr. Kuchroo first described the inhibitory receptor TIM-3, which is being exploited as a target for cancer immunotherapy. He was first to describe the development of highly pathogenic Th17 cells, which has been shown to induce multiple different autoimmune diseases in humans. He has published over 325 original research papers in the filed of Immunology and a paper describing development of Th17 authored by Dr. Kuchroo has been one of the highest cited papers in Immunology.

Dr. Kuchroo came to the United States in 1985 and was at the National Institutes of Health, Bethesda as Fogarty International Fellow for a year before joining the department of pathology at Harvard Medical School as a research fellow. He later joined the Center for Neurologic Diseases at Brigham and Women’s Hospital as a faculty member in 1992.

He obtained his degree in Veterinary Medicine from the College of veterinary medicine, Hisar, India. Subsequently, he specialized in pathology at the University of Queensland, Brisbane (Australia) where he obtained a Ph.D. in 1985. He received the Fred Z. Eager Research prize and medal for his Ph.D. research work at the University of Queensland. Based on his contributions, he was awarded the Javits Neuroscience Award by the National Institutes of Health in 2002 and the Ranbaxy prize in Medical Research from the Ranbaxy Science Foundation in 2011. He was named Distinguished Eberly lecturer in 2014 and obtained Nobel Laureate Peter Doherty lecture/prize in 2014.

Dr. Kuchroo has 25 patents and has founded 6 different biotech companies. He also serves on the scientific advisory boards of a number of big pharmaceutical companies including Pfizer, Novartis, Sanofi/Genzyme and Glaxo-Smith-Klein (GSK).

SPEAKER BIOGRAPHIES

ABSTRACT

IL-17 producing Th17 cells are distinct from TH1 or TH2 cells and have been shown to play a crucial role in the induction of multiple human autoimmune diseases including psoriasis, psoriatic arthritis, ankylosing spondylitis and multiple sclerosis. Th17 differentiation is accomplished by three overlapping steps: Induction, Amplification and Stabilization mediated by distinct cytokines. Whereas TGF-b+ IL-6 or IL-1 + IL-6 induces them, IL-21 amplifies Th17 cells, IL-23 stabilizes the phenotype of Th17 cells. Loss of any of the cytokines (TGF-β, IL-1, IL-6, IL-21 or IL-23) in the pathway results in a defect in generation of Th17. However not all Th17 cells are pathogenic and induce autoimmunity, IL-23 is a key cytokine that induces pathogenicity in Th17 cells (Lee et al., 2012). Using expression profiling at very high temporal resolution, novel computational algorithms and innovative nano-wire based “knock-down” approaches, we have developed a regulatory network that governs the development of Th17 cells. In addition to high-density temporal microarray analysis, we have performed single-cell RNA-seq of Th17 cells in order to characterize cellular heterogeneity, identify subpopulations, functional states and learn how gene expression variation affects Th17 functional states. We have identified novel regulators of Th17 cells both in vivo and in vitro that do not affect Th17 differentiation but affects pathogenic vs. non-pathogenic functional states of Th17 cells. One of the regulators CD5L (CD5like) has both cell intrinsic and cell extrinsic effects. Soluble forms of CD5L makes homo and heterodimers and regulates differentiation of Th17 cells and inhibit development of tissue inflammation and autoimmunity.

NOTES



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31

THE HUMAN SKIN MICROBIOME AND IMPLICATIONS FOR DISEASE

PROFESSOR BJORN ANDERSSONStockholm, Sweden

Björn Andersson received his PhD in 1992 and was a post-doctoral fellow at Baylor College of Medicine 1992-1995. He is now, after working as an assistant and associate professor at Uppsala University and Karolinska Institutet, a professor at the Department of Cell and Molecular Biology, Karolinska Institutet since 2007. With a background in human genetics and the human genome project, his own laboratory has focused on the study of human pathogens using genomics and bioinformatics methods. He has, for example, pioneered studies on protozoan genomes by leading the Trypanosoma cruzi genome project and viral microbiome projects (published in Science 2005, PNAS 2005, J. Virol. 2007), as well as participated in a large skin microbiome study.

ABSTRACT

The involvement of the human microbiome in disease is currently a rapidly developing field. The skin microbiome has been characterized in smaller sample sets and mainly in healthy individuals, in order to understand microbial diversity in skin homeostasis, but the relevance of microbial dysbiosis in inflammatory disease is still relatively unexplored. We have carried out the microbiome part of a large European study of the development of allergic and autoimmune skin disease, in this case atopic dermatitis and psoriasis. We have deeply sequenced skin microbial communities both by 16S sequencing and shotgun sequencing, and coupled this with transcriptome data of cutaneous gene expression in skin biopsies from the to date largest patient cohort characterized to date. The analysis of the 16S data showed that the microbiome signatures of atopic dermatitis and psoriasis samples showed clear differences from those of healthy volunteers. We were able to associate the microbiome with changes in gene expression for both diseases and identify inflammatory pathways of interest. The shotgun data has been analyzed and has deepened the analysis to include specific genes and strains as well as fungi and viruses. The analysis is still ongoing and the latest results will be discussed. These data sets provide information that can lead to the development of new biomarkers as well as new insight into factors important for skin diseases and symptoms.

SPEAKER BIOGRAPHIES

THE IMPORTANCE OF ACADEMIC-INDUSTRIAL COLLABORATION TO THE FUTURE OF MEDICAL RESEARCH

PROFESSOR SIR JOHN SAVILLLondon, UK

Professor Sir John Savill BA, MBChB, PhD, FRCP, FRCPE, FASN, FMedSci, FRS, FRSE, a clinician scientist from Edinburgh, took up the position as chief executive and deputy chair of the Medical Research Council on 1 October 2010. The appointment was initially for three years; after which it was extended until April 2016, and subsequently to 30 September 2018. He was a member of the Council from 2002 to 2008 and chaired two Research Boards during this period.

Between 2008 and 2010 John worked part-time as the chief scientist for the Scottish Government Health Directorates.

He was knighted in the 2008 New Year Honours List for services to clinical science.

John started his research career with a degree in Physiological Sciences from Oxford University in 1978, followed by degrees in Medicine at the University of Sheffield in 1981. He received a PhD from the University of London in 1989.

After junior hospital appointments in Sheffield, Nottingham and London, he spent seven years in the Department of Medicine at Hammersmith Hospital with spells as an MRC clinical training fellow and Wellcome Trust senior clinical research fellow.

In 1993, he moved to the chair of medicine, at the University of Nottingham, then in 1998 became professor of medicine at the University of Edinburgh, where he was the first director of the University of Edinburgh/MRC Centre for Inflammation Research, directing a group interested in the molecular cell biology of renal inflammation.

In 2002, John was appointed as the first vice-principal and head of the College of Medicine and Veterinary Medicine, University of Edinburgh. He retains an ongoing, research active involvement with the University of Edinburgh part time throughout his appointment as our chief executive.



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LILLY SPONSORED LECTURE

TARGETING IL-17: FINDINGS FROM RECENT CLINICAL TRIALS.

DR ANDREW BLAUVELTPortland, USA

Andrew Blauvelt hails from Portland, OR, USA, and is President and Investigator at Oregon Medical Research Center – a small company dedicated to conducting high-quality clinical studies in dermatology. A native of Michigan, Dr. Blauvelt received degrees in Electrical Engineering at Purdue University (West Lafayette, IN), and Medicine at Michigan State University (East Lansing, MI), before completing his MBA at Portland State University/Oregon Health & Science University (OHSU, Portland, OR). Dr. Blauvelt trained in dermatology at the University of Miami from 1989–1992 and in basic immunology and virology in Dr. Steve Katz’s laboratory at the National Institutes of Health (NIH) from 1992–1996. He has held senior staff positions at the NIH and more recently was Professor of Dermatology and Microbiology at OHSU and Chief of Dermatology at the Portland VA Medical Center.

Dr. Blauvelt’s clinical and research expertise spans immunology, virology, infectious diseases, psoriasis, atopic dermatitis, and biologic therapies for complex medical dermatology patients. He has published more than 200 papers and spoken globally on these topics. Dr. Blauvelt is an elected member of both the American Society for Clinical Investigation, a leading society for physician-scientists; and the International Psoriasis Council, a premier group of psoriasis experts worldwide. More recently, he has participated extensively in clinical trials assessing biologic therapies for atopic dermatitis, and has served as a lead scientific advisor for companies working in this area.

ABSTRACT

This will be an overview of recent Lilly clinical trial data. This presentation has been organised and funded by Lilly and Lilly products will be discussed in this session.

SPEAKER BIOGRAPHIES

NOTES



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35

ALMIRALL SPONSORED LECTURE

THE EPIDEMIOLOGY AND INTERRELATION OF PSORIASIS AND OTHER IL-23 RELATED DISEASES

PROFESSOR ALEXA KIMBALLBoston, USA

Alexa Boer Kimball, MD, MPH is President and Chief Executive Officer of Harvard Medical Faculty Physicians at BIDMC, Inc., an academic multi-specialty group practice with over 1200 Harvard Medical School faculty members at Beth Israel Deaconess Medical Center in Boston, Massachusetts and an additional 400 physicians based in the community . She is also President of the Beth Israel Deaconess Care Organization (BIDCO) Physician LLC which maintains a membership of approximately 2500 physicians. A Professor of Dermatology at Harvard Medical School, Dr. Kimball’s areas of research include psoriasis and hidradenitis suppurativa. She has published over 275 papers, is the author of the book “100 Questions and Answers about Psoriasis,” which has been translated into Spanish, Greek, and Korean, and editor of “Dermatologic Diseases and Cumulative Life Course Impairment.” Dr. Kimball is widely recognized for her research on physician workforce economics, quality of life, and outcomes, for which she was awarded the American Skin Association Research Award for Health Policy and Medical Education and the Mass General Hospital Bowditch Prize for increasing quality of care while reducing costs. Dr. Kimball has served on multiple non-profit Boards including: the Society for Investigative Dermatology, where she was elected Vice President, the Massachusetts Foundation for the Humanities and Public Policy, and the Hidradenitis Suppurativa Foundation. She was previously Senior Vice President of the Massachusetts General Physician Organization, which employs more than 2500 physicians, and also served as Medical Director (chief medical officer) of this organization. She is current President of the International Psoriasis Council.

ABSTRACT

The elucidation of the role of IL-23 in psoriasis and other diseases has been a fascinating story of concurrent and synergistic discovery driven by laboratory findings, translational investigation, clinical observation, and epidemiology. As has often been in the case in dermatology, clinical observation drove some of the early hypotheses. The clinical and laboratory observations that p40 inhibitors that affected both IL12 and a relatively newly recognized cytokine in a novel pathway led to clarifications that ultimately revealed the TH-17 pathway and the pivotal role of IL23. Comorbid conditions in patients with psoriasis were being described in depth in parallel and soon thereafter, genetic epidemiology confirmed a biologic basis for these relationships. Yet there appear to be interesting biologic differences between the effects across these related comorbid but disparate diseases which will be discussed. Our understanding of these differences and the fundamental biology will only improve as we observe the effects of new agents that target the p19 moiety of IL-23 and therefore are expected to have even more targeted effects in clinical practice.

SPEAKER BIOGRAPHIES

LEO PHARMA SPONSORED LECTURE

PRO-INFLAMMATORY REDUNDANCY IN THE IL-17 PATHWAY - THE ROLE OF THE INDIVIDUAL IL-17 CYTOKINE FAMILY MEMBERS IN PSORIASIS

PROFESSOR JAMES KRUEGERNew York, USA

James G, Krueger, MD, PhD is Head of the Laboratory for Investigative Dermatology at the Rockefeller University. He also serves as a Physician, Co-director, Center for Clinical and Translational Science at the Rockefeller University Hospital, and Chief Executive Officer of the Rockefeller University Hospital in New York City.

Dr.Krueger earned his bachelor’s degree from Princeton University and a PhD in virology and cell biology from the Rockefeller University. He received an MD from Cornell University Medical College, where he also completed an internship in internal medicine and residency in dermatology. Dr.Krueger is certified by the American Board of Dermatology.

His research group at Rockefeller was the first to conduct clinical trials with specific, targeted immune antagonists in psoriasis and this work established that elimination of pathogenic T-cells from skin lesions could reverse the full pathological phenotype of psoriasis. Since then his group has used immune-based therapeutics to dissect inflammatory pathways in psoriasis and to conduct parallel pharmacogenomic studies that define mechanisms of targeted therapeutics in human populations. A more recent focus has been definition of new inflammatory pathways, as well as new types of inflammatory cells in psoriasis lesions that are now being targeted with new biologic drugs. He has been an advocate of bidirectional translational research (bench to bedside and back) in humans using psoriasis as a model inflammatory disease to dissect pathogenic pathways that cannot be studied in animal models.

ABSTRACT

The interleukin-17 (IL-17) pathway is central in the pathophysiology of psoriasis as evidenced by the high levels of skin clearance achieved by therapies that directly target the IL-17 cytokine or it’s receptor. Increased expression of IL-17 cytokines, which signal through the IL-17 receptor complex directly on the surface of keratinocytes and immune cells, leads to release of pro-inflammatory mediators, resulting in inflammation and clinical manifestations of psoriasis. IL-17 is not a single cytokine, but comprises a family of 6 pro-inflammatory cytokine members: IL-17A to IL-17F. IL-17A, IL-17C, IL-17E, IL-17F and the IL-17A/F heterodimer have all been described to have a role in psoriasis.

This lecture will review the current understanding of each IL-17 family member and their role in psoriasis, presenting new transcriptomics data, and linking it to a better understanding of the pro-inflammatory redundancy in the IL-17 pathway.



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JANSSEN SPONSORED LECTURE

IL-23 INHIBITION AS A STRATEGY TO TREAT IMMUNE-MEDIATED INFLAMMATORY DISEASES

PROFESSOR JÖRG PRINZMunich, Germany

Jörg Prinz is Professor of Dermatology and Venereology at the Clinic for Dermatology and Allergology of the Ludwig-Maximilian University (LMU) in Munich, Germany. He graduated with a medical degree in 1983. After 5 years of basic immunology research as a postdoctoral fellow, he joined the Clinic for Dermatology and Allergology in 1990, where he founded the Research Group for Immunopathology. Professor Prinz earned specialist qualifications in dermatology and venerology in 1995 and in allergology in 1996, and was appointed as Full Professor of Dermatology in 2001. His current responsibilities include being deputy chair of the department and supervising the phototherapy unit and psoriasis centre, and the serological analysis laboratory. At medical school he received several rewards for his commitment to education.

Professor Prinz’s main research interest is in the analysis of the T-cell mediated immunopathogenesis of psoriasis and the identification of psoriatic autoantigens; he is also interested in developing experimental therapies for T-cell mediated autoimmune disorders, and has been actively involved in preparing evidence-based guidelines for psoriasis treatment. He has published extensively in major peer-reviewed journals.

Professor Prinz is a member of the European Academy of Dermatology and Venereology, the International Psoriasis Council, and the International Federation of Psoriasis Associations. He was the Scientific Chairman of the 2nd World Psoriasis and Psoriatic Arthritis Conference in Stockholm, Sweden, in 2009.

PROFESSOR SILVIO DANESEMilan, Italy

Silvio Danese is Head of the Inflammatory Bowel Disease (IBD) Center, Division of Gastroenterology, at Humanitas Research Hospital and Professor in Gastroenterology at Humanitas University, both in Milan, Italy. He trained in gastroenterology at Policlinico Gemelli, Rome, Italy, and earned his PhD there in 2004. Professor Danese also worked in Prof. Claudio Fiocchi’s laboratory at the Case Western Reserve University, Cleveland, OH, USA from 2001 to 2004.

His main research area of interest is the investigation of the fundamental mechanisms underlying IBD pathogenesis, while his daily clinical activity is related to IBD service. He is actively involved in many international clinical trials in IBD-related areas and has published more than 300 papers in peer-reviewed journals, including Gastroenterology, Gut, Journal of Clinical Investigation, Nature, and Journal of Immunology.

SPEAKER BIOGRAPHIES

Professor Danese is a member of many organizations related to the IBD field, including the European Crohn’s and Colitis Organisation (ECCO), where he served as Secretary from 2012 to 2015 and as President-elect from March 2016 to present. He is also Scientific Secretary for the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) and sits on the Editorial Board of Gut and Alimentary Pharmacology & Therapeutics.

ABSTRACT

The recent introduction of novel treatments targeting the IL-23/Th17 immune pathway has had major implications for our management of patients with moderate-to-severe plaque psoriasis, and potentially for management of patients with other immune-mediated inflammatory diseases (IMIDs) such as inflammatory bowel disease (IBD). Patients suffering from moderate-to-severe psoriasis now have additional treatment options that have been shown to significantly improve skin clearance and reduce the debilitating symptoms such as itch, pain, stinging, burning, and skin-tightness.

In our presentations, we will show how the effectiveness of IL-23 inhibition in treating IMIDs is based on a thorough understanding of the role of IL-23 in disease pathogenesis. Clinicians have been able to formulate effective management strategies for day-to-day clinical practice based on an understanding both of this role and of how the different IL-23 inhibitors act and where they have effect.

Our presentation will include: • The IL-23/Th17 immune pathway in psoriasis and other IMIDs: activation, differentiation, and amplification,

and the implications for patient treatment • A review of the latest clinical data on IL-23-specific inhibitors • Practical lessons learned from the use of these agents in day-to-day clinical practice

We will also address unmet medical needs in the management of IMIDs, and demonstrate how these needs can be met by IL-23 inhibition. Importantly, and uniquely, we will also offer insights from both the dermatological and gastroenterological perspectives, highlighting the benefits of a cross-specialty approach in managing IMIDs.



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FROM GWAS TO SYSTEMATIC HOST-MICROBIOME ASSOCIATION STUDIES IN COMPLEX IMMUNE-MEDIATED DISEASES

PROFESSOR ANDRE FRANKEKiel, Germany

Professor Franke’s main scientific interests are the development and establishment of novel high-throughput technologies, the inherent bioinformatic integration and application of both to identify genetic and epigenetic causes of chronic inflammatory diseases such as Crohn’s disease, ulcerative colitis, psoriasis, primary sclerosing cholangitis, and atopic eczema. Having worked on genome-wide association studies for the last years, his research agenda currently focuses on clinical data management, whole-genome and whole-exome resequencing, microbiome analyses and immunogenetics studies.

ABSTRACT

Genome-wide association (GWAS) have significantly contributed to our understanding of the etiology of chronic and complex immune-mediated diseases (CID). Inflammatory bowel diseases (IBD) with its main sub phenotypes Crohn’s disease and ulcerative colitis, are prototypic CIDs that affect about 2-3 persons out of a 1000 in Western countries. IBD shares part of its genetic and immunological background with diseases like psoriasis, ankylosing spondylitis, and primary sclerosis cholangitis. To this end, over 250 genetic susceptibility loci were identified in the past 10 years through GWAS and candidate-gene association studies. Complex immunogenetics efforts are currently being undertaken to solve CID. Still, the exact cause of most CID has not been identified and components of the gut microbiome are also likely disease-causing environmental factors for CID. In my talk I will focus on our ongoing efforts in host-microbiome association analyses and allude to the methodological challenges of these kind of analyses. I will show immunogenetics and host-microbiome interaction approaches, which could serve as a role model for psoriasis research projects.

SPEAKER BIOGRAPHIES

FROM GENOME WIDE ASSOCIATION TO FUNCTIONAL RELEVANCE

DR TUULI LAPPALAINENNew York, USA

Tuuli Lappalainen is an Assistant Investigator and Core Member at the New York Genome Center, and an Assistant Professor in the Department of Systems Biology at Columbia University. She got her PhD from University of Helsinki in 2009, and did postdoctoral research with Manolis Dermitzakis at University of Geneva, and Carlos Bustamante at Stanford University. Her research focuses on functional genetic variation in human populations and its contribution to traits and diseases. She has pioneered in integration of large-scale genome, transcriptome and epigenetic data to learn how genetic variation affects gene regulation – the largely unknown factor that underlies the majority of human diversity and disease risk. Her research group tackles these questions by both computational analysis of large data sets and experimental work using genome editing assays. She has contributed to several international research consortia in human genomics, including the 1000 Genomes Project, the Geuvadis project, and the Genotype Tissue Expression (GTEx) Project.

ABSTRACT

Detailed characterization of cellular effects of genetic variants is essential for understanding biological processes that underlie genetic associations to disease, as well as basic genome function. One approach to address this challenge is map genetic effects on the transcriptome across multiple human tissues and conditions. In this talk, I will discuss our recent work in integrating large-scale data sets of genome and transcriptome variation to understanding genetic regulatory variants, genetic effects on transcriptional response to immune stimuli, and their contribution to autoimmune and other diseases.



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WHY BIOLOGICS FAIL

PROFESSOR ANN GILSLeuven, Belgium

As a pharmacist, Ann Gils obtained her PhD in Pharmaceutical Sciences in 1997. She is a full professor at the Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium. The core technology of the laboratory is the development of monoclonal antibodies and antibody fragments with the aim to develop these antibodies either as therapeutics or as diagnostics.

In the past few years, she has developed and validated a number of assays to measure the serum and anti-drug antibody concentrations of biologicals (infliximab; adalimumab; etanercept, golimumab, vedolizumab, secukinumab and ustekinumab) and has participated in Therapeutic Drug Monitoring studies in the field of gastroenterology, rheumatology and dermatology. Through PKPD modeling, she studies the effect of co-variates on PK and PD. She has published more than 200 papers in the field of thrombosis and therapeutic drug monitoring of biologicals.

ABSTRACT

Chronic inflammatory diseases such as rheumatic diseases, spondyloarthritis, inflammatory bowel diseases and plaque psoriasis have a high prevalence and typically start early in life, thereby strongly affecting the quality of life and productivity of young and active individuals. Patients have to be treated life-long and this requires safe, tolerable and cost-effective treatments. The introduction of biologics has revolutionized the short- and long-term outcome of patients with chronic inflammatory diseases. Unfortunately, 10-30% of patients (primary non-response) will not respond to treatment and 30-60% of patients initially responding will lose clinical benefit during treatment (secondary loss of treatment). Primary non-response is defined as a lack of clinical response to the treatment, assessed 8-12 weeks after initiation. It is believed that this primary non-response is mainly driven through mechanistic override of the disease. Another explanation is that primary non-response is caused by non-sufficient exposure to the drug. A drug can only exert its pharmacological effect when adequate concentrations of drug are achieved in the circulation and at the drug’s site of action. Inter-and intra-individual differences in bioavailability and pharmacokinetics may contribute to the problem of insufficient exposure. Secondary loss of response is defined as a loss of clinical benefit after initially responding to the drug. The secondary loss of response can either be attributed to disease-related factors or drug-related factors such as the formation of anti-drug antibodies.

SPEAKER BIOGRAPHIES

In inflammatory bowel diseases and rheumatoide arthritis patients, it has recently been shown that adequate serum concentrations of biologics are associated with sustainable clinical response. Pharmacological guidance using drug concentrations of biologics is emerging in European countries as a valuable tool for clinical decision making and growing evidence suggests that monitoring drug concentrations and anti-drug antibody concentrations together with clinical response also allows a better management of patients with plaque psoriasis. A growing body of evidence demonstrates an exposure-response association for psoriasis patients treated with infliximab, adalimumab and to some extent for ustekinumab. For etanercept, an age-dependent association between exposure and psoriasis severity was recently reported.

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BIOLOGY AND PATHOLOGY OF IL-36

DR JENNIFER TOWNESan Diego, USA

Dr. Towne completed her doctoral degree in the Department of Molecular Genetics, Biochemistry, and Microbiology at the University of Cincinnati School of Medicine where she studied the role of aquaporins in pulmonary inflammation and edema. She subsequently joined Immunex as a post-doctoral fellow investigating the role of novel IL-1 family members in physiology and pathophysiology. Dr. Towne was hired at Immunex as a full time scientist and worked at Immunex/Amgen for 13 years focusing first on the biology of IL-1 family members, primarily IL-36, IL-17 family members, and IL-23 in the skin, lung and gut. She led or was a key contributor to multiple large and small molecule project teams currently in clinical development for psoriasis and inflammatory bowel disease (IBD). For the last several years she was responsible for developing the strategy and leading the IBD discovery team at Amgen. Dr. Towne started at Janssen in November 2014 as Scientific Director, Immunology Discovery, where she was responsible for the IBD discovery efforts on the West coast. Dr. Towne is currently the discovery lead for the IBD disease area stronghold across Janssen where she is responsible for discovery efforts to develop innovative therapeutics for the treatment, prevention and cure of IBD. Dr. Towne is a longstanding member of the International Cytokine and Interferon Society (ICIS) and has served as the co-chair of the awards committee and of the publication committee.

ABSTRACT

IL-36α, IL-36β and IL-36γ are members of the IL-1 family of cytokines that signal through a common receptor composed of IL-36R and IL-1RAcP to activate NFκB and mitogen activated protein kinases such as p38 and JNK and promote inflammatory responses. IL-36Ra is a natural antagonist of the three IL-36 agonists that binds to IL-36R, inhibits binding of the agonistic ligands, does not recruit the co-receptor IL-1RAcP and does not stimulate any intracellular responses. These cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells and fibroblasts. Processing of the N-terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response and is implicated strongly through both functional and genetic evidence in the pathology of psoriatic disorders. Emerging data also suggests a role for this cytokine family in pulmonary and intestinal physiology and pathology. Although much has been learned about the biochemistry of IL-36 and its role in various tissues, it is clear that we are at an early stage in our understanding of the full biology of these cytokines.

SPEAKER BIOGRAPHIES

NOTES



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ABBVIE SPONSORED LECTURE

THE EVOLUTION OF T CELL TARGETED THERAPY IN PSORIASIS

PROFESSOR JONATHAN BARKERLondon, UK

Jonathan Barker is Professor of Medical Dermatology and Head of St John’s Institute of Dermatology, King’s College London and honorary consultant dermatologist at Guy’s and St. Thomas’s Hospitals. He specialises in complex hospital based medical dermatology. He is co-director of the severe psoriasis service and Skin Therapy Research Unit. His research extends from genetic discovery through to clinical outcome measurement. It has been funded from multiple sources including European Union, Medical Research Council (MRC UK), National Institute for Health Research, medical charities and industry. He is a key investigator in national and international consortia aiming to identify genetic susceptibility to important chronic skin diseases such as psoriasis, acne and eczema and in biomarker discovery of outcomes to interventions.

Professor Barker is course director of the Institute’s MSc Clinical Dermatology for overseas graduates. This internationally renowned course has existed for more than 40 years and has helped train many dermatologists around the globe extending from the Caribbean through Africa to the Middle and Far East.

Professor Barker has published over 250 peer-reviewed papers, authored and edited several books including the new edition of the ‘Rook Book’- the most comprehensive textbook in the English language. Highly cited publications include those in the Lancet, Nature Genetics and New England Journal of Medicine. He sits on the editorial boards of several dermatology journals. He has delivered plenary keynote lectures at many meetings internationally including Dohi Memorial Lecture at Japanese Dermatology Association in 2016 and Eugene M Farber Oration at Society for Investigative Dermatology, USA in 2017. He is a past President of the European Dermatology Forum and the European Society for Dermatological Research. He is currently President-elect of the International Psoriasis Council. He is an honorary overseas member of the several national dermatological associations including Denmark, Germany, Japan and the USA.

ABSTRACT

Over the last thirty years, in-depth research has revolutionised our understanding of the immunopathogenesis of psoriasis, leading to the discovery of new therapeutic targets and evolving the way we manage our patients. Moving target identification from serendipity to science-driven mechanistic rationale, the development of T cell-targeted therapies has brought new innovations to the management of psoriasis. These innovations have resulted in dramatic clinical advances and have equally created new questions that demand further research. In this lecture, Professor Jonathan Barker will take the audience through a review of the past, present and future of T cell-targeted therapies for psoriasis.

SPEAKER BIOGRAPHIES

As our perception of psoriasis shifted from a skin disease to a systemic, T cell-driven condition involving multiple cytokines, research shone new light onto the recurrent nature of lesions and the psoriasis pathogenesis model. The union of immunology and genetics, enabled the introduction of more specific targeted therapeutic agents, able to alter the T-cell-driven inflammatory cascade associated with T cell activation.As we advance our understanding of psoriasis, we continue to identify even more specific targeted T cell therapies. The potential of IL-23 p19 inhibition underpins one of the latest innovations in psoriasis and may change the way psoriasis is currently managed.

The clinical landscape of psoriasis is changing rapidly, with the introduction of biosimilars alongside the development of new agents with new modes of action, with results that may not be fully explained by our current understanding of the disease.

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UCB PHARMA SPONSORED LECTURE

RE-EVALUATING THE ROLE OF IL-17F IN IMMUNE-MEDIATED CHRONIC INFLAMMATION: DUAL NEUTRALISATION OF BOTH IL-17A AND IL-17F AS A NOVEL TARGETING APPROACH IN PSORIATIC DISEASES

DR STEVAN SHAWSlough, UK

Stevan Shaw joined Celltech in 1993 as a research graduate in the immunology therapeutic area. Whilst an employee, he completed his immunology PhD training at Imperial College London focusing on lymphocyte biology; specifically, in vivo functions of Th1 and Th2 cells. Post-PhD training Stevan completed a sabbatical in the USA working in the immunology target discovery department where he designed, developed and implemented in vivo immunology screens for target identification and validation for autoimmune diseases. Post acquisition of Celltech by UCB, Stevan has gained a thorough understanding of antibody-based therapeutics leading projects within the UCB preclinical immunology portfolio and in his functional role as Head of Preclinical Pharmacology. In 2012, Stevan took on the role of leading the UCB4940 clinical programme through to Phase 2b and is now responsible for scientific research to further the understanding of how targeting IL-17A and IL-17F biology may translate into patient value.

ABSTRACT

Identification of immunological pathways pivotal in the pathogenesis of immune-mediated chronic inflammation has led to the development of treatments targeted against key pro-inflammatory cytokines (e.g., TNF, IL-17A and IL-23).1,2 While the benefit of current therapies is evident, achieving and maintaining complete skin clearance remains a challenge; therefore, treatments targeting other mediators of inflammation could provide additional patient value.

Historically, the most extensive research into the IL-17 family of cytokines (IL-17A, IL-17B, IL-17C, IL-17D, IL-17E [also known as IL-25] and IL-17F) has been focused on strategies for the inhibition of IL-17A. However, the role of IL-17F, which shares approximately 50% structural homology and overlapping biological function with IL-17A, has been re-evaluated based on recent insights from murine and human data that suggest it may also play an important role in psoriatic diseases. In this talk, we will discuss the contribution of IL-17F to immune-mediate chronic inflammation and describe the preclinical and early clinical data supporting dual neutralisation of IL-17A and IL-17F as a novel targeting approach in psoriatic diseases.

SPEAKER BIOGRAPHIES

In lesional skin tissue and inflamed synovium from patients with psoriatic arthritis (PsA), similar patterns of expression and upregulation have been demonstrated for IL-17A and IL17F. Moreover, in preclinical models, both IL-17A and IL-17F co-operate with other pro-inflammatory cytokines, such as TNF, amplifying inflammatory responses in a qualitatively similar manner. Dual neutralisation of IL-17A and IL 17F in disease-relevant human cellular systems resulted in reduced expression of inflammation-linked genes and pro-inflammatory cytokines and greater suppression of immune cell migration when compared with IL-17A blockade alone. These data suggest that IL-17F plays an important role in chronic inflammation, beyond that of IL-17A.

IL-25, another member of the IL-17 family of cytokines which is implicated in Th2 responses, which shares a receptor subunit with IL-17A and IL-17F, has been found to indirectly modulate pro-inflammatory cytokine production. Targeted dual neutralisation of IL-17A and IL-17F, without interfering with the function of IL-25, may therefore produce optimal inhibition of IL-17-mediated inflammatory signalling responses in psoriatic diseases.

Given the evidence to support a role for both IL-17A and IL-17F in driving immune-mediated inflammatory diseases, rational design was utilised to generate UCB4940, a humanised immunoglobulin G1 monoclonal antibody that has strong affinity for both cytokines.

The therapeutic potential of UCB4940 has been evaluated in a first-in-human study in patients with mild psoriasis and a proof-of-concept study in patients with moderate-to-severe PsA. In these studies, UCB4940 was associated with a rapid onset of clinically meaningful efficacy and sustained reductions in disease activity measures, with no unexpected safety signals. These preliminary findings suggest that dual neutralisation of IL-17A and IL-17F with UCB4940 may offer a further approach in the treatment of psoriatic diseases.

1. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361:496–509.2. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007;445:866–73.



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NOVARTIS SPONSORED LECTURE

DISEASE MODIFICATION, FROM BEDSIDE TO BENCH

PROFESSOR LARS IVERSENAarhus, Denmark Lars Iversen is the Head of the Psoriasis Clinic at the Department of Dermatology, Aarhus University Hospital and Professor of Dermatology at Aarhus University, Denmark, where he received his medical degree in 1991. In addition to his teaching duties at Aarhus University, Professor Iversen serves as a reviewer of PhD dissertation and doctoral theses at several European institutes.

Professor Iversen has authored more than 160 publications in peer-reviewed journals and is a reviewer for several medical journals including the Nature Immunology, Proceedings of the National Academy of Sciences, the EMBO Journal and Blood. Professor Iversen has received several prizes including the Nordic Prize of Dermatology and Venereology in 2001 and Advances in Psoriasis in 2008. His research interests include all aspects of psoriasis ranging from molecular biology and epidemiological studies, to clinical research. In addition, he is currently conducting research in cutaneous T-cell lymphomas.

ASSOCIATE PROFESSOR LIV EIDSMOStockholm, Sweden

Group leader at Department of Medicine, Karolinska Institutet and practicing dermatologist at Karolinska University Hospital in Sweden. Liv Eidsmo received her MD 1999 and a PhD in Immunobiology in 2006, both from Karolinska Institutet. Following a postdoc in Frank Carbone’s laboratory at Melbourne University, Liv Eidsmo established her own research group in 2010 in Mona Ståhle’s laboratory at Karolinska Institutet and became a board-certified dermatologist in 2017. Dr Eidsmo is a Wallenberg Clinical Fellow, a Ragnar Söderberg Fellow of Medicine and was recently awarded the Ellis and Ivar Janzen prize from the Swedish Society of Medicine.

Dr Eidsmo’s research focus on resident immune cells in human skin. The group recently defined functionally distinct subsets of tissue resident memory T (TRM) cells based on the expression of the integrin CD49a and have characterized pathogenic TRM cells in vitiligo and psoriasis.

SPEAKER BIOGRAPHIES

ABSTRACT

Could early intervention in psoriasis result in and disease modification?Professor Lars IversenAarhus, Denmark

Most published guidelines for the treatment of psoriasis recommend the conventional step-up treatment approach starting with topical treatment and followed by narrow band UVB and/or systemic treatment if the disease is not well controlled. Thus, in recent years there has been an evolving hypothesis in some immune mediated inflammatory diseases like rheumatoid arthritis and Crohn’s disease suggesting that early intensive treatment with biologic drugs can dampen the immune mechanisms that lead to a chronic inflammation. This early and more aggressive treatment approach has been shown to significantly improve long-term outcomes in disease activity in these diseases. 1,2

In this symposium, we will discuss the scientific rational behind the hypothesis that early and more intensive intervention in subjects with new-onset moderate to severe plaque psoriasis may lead to superior outcomes and lasting benefits compared to the traditional step-up treatment approach.

Involvement of skin-resident T cells in relapsing psoriasis.Associate Professor Liv EidsmoStockholm, Sweden

Tissue resident immune cells are crucial components barrier immunity and the human skin harbours a heterogeneous pool of resident memory T (Trm) cells. We recently reported that CD49a marks CD8+ T cells poised to cytotoxicity and IFN-gamma production, while IL-17 producing T cells lacks CD49a-expression in healthy skin. The balance of functionally distinct subsets of resident memory T (Trm) cells is altered in human inflammatory skin diseases. In psoriasis, Trm cells poised to IL-17 are enriched and these cells persist in clinically resolved lesions. Following ex vivo activation, Trm cells from active and resolved psoriasis lesions induce pathogenic tissue responses capable of steering focal pathology 3. Furthermore, pathogenic Trm cell responses are associated with short time in remission following UVB treatment. An ongoing study may offer a possibility to test if the composition and functionality of Trm cells steer recurrent psoriasis in a clinically relevant setting 4.

In this symposium, the pathogenic properties of Trm cells in psoriasis and how early intervention may prevent disbalances in the set-up of Trm cells afflicted skin will be discussed.

References:

1 Smolen et al. Ann. Rheum. Dis. 76; 960–9772 Danese et al. Gut 2017; 0, 1-93 Cheuk et al J Immunology 2014 and Cheuk et a Immunity 2017.4 https://clinicaltrials.gov/ct2/show/NCT03020199?cond=stepin+study&rank=1



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CELGENE SPONSORED LECTURE

THE COMPLEX MANAGEMENT OF PATIENTS WITH PSORIASIS AND COMORBIDITIES: THE ROLE OF THERAPY CHOICE

PROFESSOR PAOLO GISONDIVerona, Italy Professor Paolo Gisondi began his clinical career at the Catholic University of the Sacred Heart in Rome, Italy, where he graduated in Medicine in 1997 and in Surgery in 1998. Subsequently, he worked as a doctor in Rome at the San Gallicano Dermatological Institute-IRCCS and at the Institute of the Immaculate Dermopatico-IRCCS, taking care of hospitalised patients. He specialised in Dermatology and Venereology in 2002 at the Dermatology Clinic of the University of Parma, Italy.

Professor Gisondi began his scientific work at the Institute of the Immaculate Dermopatico-IRCCS, where he was actively involved in clinical dermatology through planning and participation in epidemiological studies, and studies on quality of life in psoriasis, psoriatic arthritis and atopic dermatitis, collaborating with Professor G. Girolomoni. At the same time, he participated as a sub-investigator in research protocols, mainly on clinical biologics in the treatment of psoriasis, and topical calcineurin inhibitors in atopic dermatitis. Since 2005, he has worked at the Dermatology Clinic of the University of Verona, Italy, where he is involved in the design and implementation of epidemiological studies to assess the association between psoriasis and the metabolic syndrome, and therapeutic impact of psoriasis intervention by correcting the underlying metabolic disorders.

ABSTRACT

The clinical presentation of chronic plaque psoriasis is highly variable among patients because of factors such as the age of onset, the involvement of different areas and the severity of the disease. In addition, approximately 40% of patients develop psoriatic arthritis.1 Other comorbidities are also frequently associated with the disease, including metabolic syndrome, obesity, type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular disease.

It is likely that genetic, metabolic and environmental factors contribute to comorbidities in psoriasis patients.2

In particular, emerging evidence suggests that psoriasis and metabolic syndrome share similar pathogenic pathways.2 In this context, adipose tissue has received special attention because of its role as an active endocrine and paracrine organ involved in lipid and glucose metabolism and in the regulation of inflammation.2

SPEAKER BIOGRAPHIES

Psoriasis is a chronic disease with an unpredictable natural history that requires long-term treatment. The presence of comorbidities in psoriasis patients can bring additional levels of complexity to treatment decisions. The long-term use of treatments for psoriasis should take into account this complex picture, and consequently, treatment approaches should be personalised according to the specific characteristics and needs of the patient.3

These elements should be considered in order to achieve optimal care.2

References

1. Husted JA, et al. Arthritis Care Res (Hoboken) 2011;63:1729–1735.2. Gisondi P, et al. Clinics in Dermatology 2017 [Epub] doi: 10.1016/j.clindermatol.2017.09.005.3. World Health Organization - Global report on psoriasis. Available at: http://apps.who.int/iris/ bitstream/10665/204417/1/9789241565189_eng.pdf (Accessed October 2017)

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CHALLENGING CONVENTIONAL CLASSIFICATION DOGMA: TOWARDS A NEW CLINICAL TAXONOMY OF PSORIASIS

PROFESSOR ULRICH MROWIETZKiel, Germany

Professor Ulrich Mrowietz is a Dermatologist and Head of the Psoriasis Center at the University Medical Center Schleswig-Holstein, Campus Kiel.

His main scientific and clinical interests are psoriasis and psoriasis management. His recent research focuses on trigger factors for psoriasis, pustular psoriasis and the mechanisms of action of fumarates. He has worked on establishing management procedures for psoriasis that have been included in the first Global Report on Psoriasis by the WHO.

Professor Mrowietz serves as the Editor-in-Chief of the Archives of Dermatological Research. He is an active member of the cluster of excellence “Inflammation at Interfaces” at the University of Kiel, a former member of the Executive Board of the German Dermatological Association (2007-2015), as well as a member of the Scientific Advisory Board of the German Psoriasis Association. He is also a member of numerous national and international Dermatological Societies and a co-author of the German and European Guidelines for the treatment of psoriasis and lead the European Consensus Programme on Treatment Goals in psoriasis. Professor Mrowietz has published more than 270 articles referenced in the Medline data base, and has written numerous chapters in textbooks including “Fitzpatrick’s Dermatology in General Medicine” and Braun-Falco’s “Dermatologie und Venerologie”.

ABSTRACT

Although psoriasis as a disease entity is known since more than hundred years the understanding of its pathogenesis and genetic background is still insufficient as well as their value to the predict the clinical course of disease and response to treatment.

It is of note that the clinical appearance of psoriasis is heterogeneous and in the past a large number of clinical subtypes have been described. Until today there is no international consensus regarding the nomenclature of a clinical classification of psoriasis. Generation of a consensus is hampered by a varying phenotype in different ethnic groups, diverse textbook descriptions and country-specific peculiarities. Phenotypic variability of psoriasis lesions exists not only among different individuals but also within the same patient during the disease course and after trigger factor-induced exacerbations.

SPEAKER BIOGRAPHIES

It is accepted in the dermatological community to separate pustular from non-pustular psoriasis, and early-onset from late-onset disease. However, plaque psoriasis, the prototype of non-pustular psoriasis, may show pustular eruptions during flares. Genetic studies have shown that HLA-C*0602 shows strongest association to plaque psoriasis and may explain at least in part an autoimmunological background of the disease. However, many patients with severe psoriasis lack this genetic marker.

It has been conclusively demonstrated that a number of conditions are associated with psoriasis including psoriatic arthritis, diabetes mellitus, hypertension, dyslipidemia and obesity. The latter represents an independent risk factor for psoriasis and the influence of obesity on the course of disease may be more important as compared to genetic markers.

A consensus definition of the different psoriasis phenotypes and their relation to genetic markers as well as to comorbidity is a major challenge. One initiative, the global psoriasis atlas, may be helpful to generate an inventory of psoriasis phenotypes across different ethnic groups and countries. Together with information about genotype and comorbidity this may help to generate a first unifying clinical taxonomy of psoriasis. As genetic markers and other measures to predict treatment outcomes particularly using targeted therapies have failed so far a more sophisticated clinical definition of psoriasis may fill this gap.

NOTES



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55

THE PRICE AND VALUE OF BIOLOGIC DRUGS

DR JACK SCANNELLEdinburgh, UK Jack Scannell is co-head European Pharmaceuticals, Investment Research, at UBS Investment Bank. Prior to joining UBS in 2016, Jack consulted to the drug and biotech industry, and to public sector bodies, on R&D productivity and drug pricing. He also conducted academic research on R&D productivity and remains an Honorary Fellow at the University of Edinburgh, and an Associate of CASMI at Oxford University. From 2012 to 2014, Jack was Head of drug discovery at a e-Therapeutics PLC, a bio-informatics based biotechnology firm, that sought to exploit analytic methods he had worked on as an academic, in the late 1990s. From 2005 to 2012, Jack was an investment analyst. He led the European Healthcare team at Sanford Bernstein in London. He has a degree in Medical Sciences from Cambridge University and a PhD in Physiology (Computational Neuroscience) from Oxford University.

ABSTRACT

If I offered to buy your shoes you would think I was strange, but we could probably haggle a price. If I offered to buy your children, we would not get to the haggling stage. The difference between trading shoes and children is not merely legal. It is also moral. People find it unpalatable, even taboo, to put prices on things that we treat as absolutes; life, liberty, or health. People have moral qualms about the cost of medicines for the genuinely sick, but not about the cost of Botox or liposuction. Yet medicines do not exist in a parallel universe, free from economics. Taxes are paid, as are health insurance premiums; healthcare budgets are set; doctors earn money; professors seek riches as biotech entrepreneurs; venture capitalists gamble other people’s money on the professors’ ideas; drug companies pay wages to employees and dividends to shareholders. Moral queasiness tends to reduce the quality of, and polarize, public debate on drug pricing. “Cost”, “value”, “power” and “prizes” are four ways that people think, talk or write about the mechanism by which drugs are priced. “Cost” refers to cost-based pricing; the idea that the price of goods is based on how much it costs to produce them. “Value” refers to value-based pricing; the idea that the price of goods reflects their value to the buyer. “Power” is the exercise of intellectual property rights, to create scarcity and to find the maximum price that the market will bear. “Prizes” are the incentives provided by profit tomorrow, made credible by profit today, for investors gambling on the R&D that might create tomorrow’s drugs. At present, “Value” seems the intellectually fashionable approach. In the talk, I will argue that value-based pricing appeals to the drug industry and some health economists, but that it can be bad public policy.

SPEAKER BIOGRAPHIES

NOTES



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57

SYSTEMS MEDICINE, BIG DATA AND SCIENTIFIC WELLNESS ARE TRANSFORMING HEALTHCARE

DR LEROY HOODSeattle, USA

Dr. Leroy E. Hood graduated from the Johns Hopkins University School of Medicine in 1964 with an MD and from Caltech with a PhD in biochemistry in 1968. After three years as a Senior Investigator at NIH, his academic career began at Caltech, where he and his colleagues developed the DNA gene sequencer and synthesizer, and the protein synthesizer and sequencer–four instruments that paved the way for the successful mapping and understanding of the human genome. A pillar in the biotechnology field, Dr. Hood has played a role in founding fifteen biotechnology companies including Amgen, Applied Biosystems, Integrated Diagnostics and Arivale. He is a member of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. Of the more than 6,000 scientists world-wide who belong to one or more of these academies, Dr. Hood is one of only fifteen people nominated to all three. Dr. Hood has co-authored numerous textbooks in biochemistry, immunology, molecular biology and genetics, as well as a popular book on the human genome project, The Code of Codes and he is just finishing up a text on systems biology. He is the recipient of numerous national and international awards, including the Lasker Award for Studies of Immune Diversity (1987), the Kyoto Prize in advanced technology (2002), the Heinz Award for pioneering work in Systems Biology (2006), and the coveted NAE 2011 Fritz J. and Delores H. Russ Prize for developing automated DNA sequencing. In addition to having received 17 honorary degrees from prestigious universities in the U.S. and abroad, Dr. Hood has published over 750 peer-reviewed articles and currently holds 36 patents. In 2013, he received the National Medal of Science from President Obama. Hood has been named by The Best Schools as one of the 50 Most Influential Scientists in the World Today (2014) http://isb.io/top50. Scientific American has named Hood as one of the top 6 in their selection of 100 biotech visionaries world-wide (2015) http://isb.io/visionary.

ABSTRACT

Systems medicine, the application of systems approaches to disease, places medicine at a fascinating tipping point—promising a revolution in the practice of healthcare. I will discuss how systems biology approaches have framed systems medicine and I will discuss some of the new systems-driven technologies and strategies that have catalyzed this tipping point. Moreover, four converging thrusts—systems medicine, big data (and its analytics), the digitalization of personal measurements and patient-activated social networks—are leading to a proactive healthcare that is predictive, personalized, preventive and participatory (P4). I will contrast P4 healthcare with contemporary medicine and discuss its societal implications for healthcare. P4 healthcare has two central thrusts—wellness and disease.

SPEAKER BIOGRAPHIES

I will discuss our successful effort to introduce P4 healthcare into the current healthcare system with a P4 pilot program on scientific wellness—a longitudinal, high-dimensional data cloud study on each of 108 well patients over 2014. The preliminary results both with regard to data analyses and patient responses from these studies are striking. They point to the emerging discipline of scientific wellness—and the fact that it will catalyze several new thrusts in healthcare: 1) optimizing wellness, 2) identifying the earliest disease transitions for all common diseases and learning how to reverse them and 3) employing the dense, dynamic, personal data cloud approach to study diseases (e.g. cancer, Alzheimer’s, diabetes) and their responses to therapy. Scientific wellness will also pioneer N=1 experiments to deconvolute the staggering complexity of human biology and disease. We started Arivale, a company focused on scientific wellness for the consumer, in 2015 and already have about 4000 individuals enrolled. I will also discuss some preliminary results from the Arivale studies.

My institute, the Institute for Systems Biology (ISB), in 2016 affiliated with Providence St. Joseph Health to become its research arm and I became its Chief Science Officer. Providence is one of the largest non-profit healthcare systems in the US—and ISB/Providence will be initiating a series of “translational pillars” moving applications of systems (P4) medicine from the bench to the bedside. These pillars include scientific wellness, bringing scientific wellness to cancer survivors, making Alzheimer’s a reversible and preventive disease, rather than a relentlessly progressive disease, taking a systems approach to type 2 diabetes and exploring how the deep, dynamic, personal data clouds can be used to gain a deep understanding of glioblastoma and provide new diagnostic and therapeutic approaches to this inevitably fatal tumor. It is fair to say that dense, dynamic, personal data clouds followed longitudinally on hundreds of thousands of patients/consumers will allow us to see the earliest wellness to disease transitions for all of the common cancers—and generate biomarkers for early detection and identify the drug targets or strategies (e.g., immunotherapy) that will allow us to reverse the disease before it ever manifests itself as a disease phenotype. Systems medicine, P4 healthcare and scientific wellness will open up powerful new approaches to dealing with diseases of the skin—including psoriasis.

Thus scientific wellness will catalyze a transformation in contemporary healthcare and it will provide eventually millions of dense, dynamic, personal data clouds that will present striking new opportunities for pharma, biotech, nutrition and diagnostic companies to identify biomarkers and drug target candidates. As the cost of the assays for the dense, dynamic, personal data clouds decline dramatically; scientific wellness can be brought to the developing world leading to a democratization of healthcare unimaginable even a few years ago.



from gene to clinic

59ABSTRACTS

ABSTRACTSBJD

British Journal of Dermatology

Psoriasis Gene to Clinic, 8th International Congress. TheQueen Elizabeth II Conference Centre, London, U.K.,30th November – 2nd December 2017

Free communicationsFC01Psoriasis and risk of malignant lymphoma:a population-based cohort studyM. Kamstrup, L. Skov, C. Zachariae, J. Thyssen andA. EgebergDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital,

Hellerup, DenmarkPsoriasis is a chronic proliferative inflammatory skin disease.

Epidemiological studies have suggested an association between

psoriasis and lymphoma, but data are limited. The aim of the

study was to quantify the 5-year risks of new-onset Hodgkin

lymphoma (HL), non-Hodgkin lymphoma (NHL) [excluding

cutaneous T-cell lymphoma (CTCL)] and CTCL in patients with

psoriasis. We performed a Danish nationwide cohort study

including data on all individuals aged ≥ 18 years between 1 Jan-

uary 2008 and 31 December 2012. Incidence rates (IRs) per

10 000 person-years for HL, NHL and CTCL were calculated,

and hazard ratios (HRs) with 95% confidence intervals (CIs)

were obtained using Cox regression analysis and adjusted for

age, sex, socioeconomic status and systemic treatment. The pso-

riasis cohort was stratified according to severity by systemic

antipsoriatic therapy. In total 58 138 patients with psoriasis and

4 303 731 general population controls were identified. The IRs

in patient with psoriasis for HL (IR 1.02, 95% CI 0.70–1.47),NHL (IR 4.04, 95% CI 3.36–4.87) and CTCL (IR 0.44, 95% CI

0.25–0.77) were higher among patients with psoriasis than in

the general population. Adjusted HRs revealed significant associ-

ations between psoriasis and HL (HR 1.50, 95% CI 1.01–2.23)but not NHL (HR 1.02, 95% CI 0.84–1.24) or CTCL (HR 1.66,

95% CI 0.88–3.13). When stratified by disease severity, adjusted

HRs were significant for mild psoriasis and HL (HR 2.08, 95%

CI 1.38–3.15) and for severe psoriasis and NHL (HR 1.64, 95%

CI 1.12–2.40) and CTCL (HR 13.63, 95% CI 6.72–27.64). Inconclusion, patients with severe psoriasis have a higher co-

occurrence of NHL and especially CTCL than the general popula-

tion. Patients with mild psoriasis have a slightly increased risk of

HL. The relative contributions of an initial incorrect diagnosis,

possible overlap in disease pathogenesis, and complications of

systemic medication need further investigation.

FC02Developing a therapeutic range and predictingresponse to biologics in patients with psoriasis: amulticentre prospective observational cohort studyT. Tsakok and the PSORT ConsortiumKing’s College London and St John’s Institute of Dermatology, London, U.K.

Biological therapies have transformed treatment in immune-

mediated inflammatory diseases, yet significant numbers of

patients experience treatment failure. Variability in drug levels

correlates with outcomes across multiple inflammatory dis-

eases, but with limited data in psoriasis. In this prospective

observational cohort study (60 dermatology specialist centres)

we determine the clinical utility of therapeutic drug monitor-

ing using the exemplar tumour necrosis factor antagonist

adalimumab. Adults (n = 515) recruited to Biomarkers of Sys-

temic Treatment Outcomes in Psoriasis (BSTOP) within the

biologics pharmacovigilance British Association of Dermatolo-

gists Biologic Interventions Registry (BADBIR) with serial

adalimumab level measurements up to 1 year were included

(888 samples; 63% male; mean age 44 � 12 years).

Response to treatment at 6 months was defined as ≥ 75%

improvement in Psoriasis Area and Severity Index (PASI 75;

primary outcome). We found that drug level can discriminate

responders from nonresponders with a minimally effective

adalimumab level identified as 3.3 lg mL�1 [sensitivity 80%;

specificity 57%; area under the curve 0.73, 95% confidence

interval (CI) 0.67–0.79]. Multilevel mixed-effect logistic

regression modelling to account for clustering of samples

within patients, and to adjust for covariates, indicates that a

target drug level of 7 lg mL�1 will achieve a minimum 80%

probability of response (81%, 95% CI 76–86). Early serum

drug level was confirmed as an additional independent indica-

tor of 6-month PASI 75 response [OR(√drug level) 1.95, 95%

CI 1.06–3.57, P = 0.031] and PASI 90 response [OR(√drug

level) 2.38, 95% CI 1.26–4.50, P = 0.008], substantially

improving the model’s goodness of fit. Smoking and disease

duration were also key baseline predictors influencing

interindividual variation. This real-world study with pragmatic

drug level sampling provides strong evidence to support

proactive measurement of drug levels in the management of

psoriasis, and highlights the importance of taking drug levels

into account when searching for biomarkers of treatment

response.

FC03The differential production of interleukin (IL)-26 vs.IL-17 by T helper 17 cells contributes to thedevelopment of different forms of psoriasisA. Fries, J. Di Domizio, O. Demaria and M. GillietUniversity Hospital Lausanne, Lausanne, SwitzerlandInterleukin (IL) 17-producing helper T cells (Th17 cells) play

a role in protection against infections and have also been

linked to autoimmune diseases like psoriasis. Th17 cells pro-

duce IL-17A/F, IL-22 and IL-26. Whereas the induction of

© 2017 British Association of Dermatologists British Journal of Dermatology (2017) 1

IL-17 and IL-22 expression during Th17 differentiation has

been well described, the mechanism regulating the production

of IL-26 remains ill defined. Here, we found that IL-6 alone is

required to generate IL-26-producing T cells from naive T

cells, but it is not sufficient to induce IL-17-producing T cells.

By contrast, the generation of IL-17-producing T cells required

the presence of IL-1 and IL-23, which are unable to induce

IL-26, suggesting that Th17 cells comprise two distinct sub-

sets, namely IL-26-producing T cells and IL-17-producing T

cells. Although all Th17 cytokines are elevated in psoriasis, we

also found a dichotomy between IL-17 and IL-26 expression

in the skin of different forms of the disease. Whereas IL-17

was mainly associated with chronic plaque psoriasis, IL-26

appeared to be strongly expressed in more acute lesions (ery-

throdermic psoriasis, guttate psoriasis, paradoxical psoriasis).

Importantly, the expression of IL-26 in psoriasis correlated

with the expression of IL-6 but not IL-1 nor IL-23, indicating

that the presence of IL-26-producing T cells may drive the

development of acute skin inflammation. These findings there-

fore identify IL-26 as a novel therapeutic target for the treat-

ment of acute forms of psoriasis.

FC04Psoriasis-associated late cornified envelope)proteins have antibacterial activityH. Niehues,1 L. Tsoi,2,3,4 D. van der Krieken,1

P. Jansen,1 M. Oortveld,1 D. Rodijk-Olthuis,1 I. vanVlijmen-Willems,1 W. Hendriks,5 R. Helder,6

J. Bouwstra,6 R. Mesman,7 L. van Niftrik,7 E. van denBogaard,1 P. Stuart,2 R. Nair,2 J. Elder,2,8

P. Zeeuwen1 and J. Schalkwijk11Department of Dermatology and 5Department of Cell Biology, Radboud

University Medical Centre, Radboud Institute for Molecular Life Sciences,

Nijmegen, the Netherlands; 2Department of Dermatology, 3Department of

Computational Medicine and Bioinformatics and 4Department of Biostatistics,

University of Michigan, MI, U.S.A.; 6Leiden Academic Center for Drug

Research, Department of Drug Delivery Technology, Gorlaeus Laboratories,

Leiden University, Leiden, the Netherlands; 7Department of Microbiology,

Institute for Water and Wetland Research, Faculty of Science, Radboud

University, Nijmegen, the Netherlands and 8Ann Arbor Veterans Affairs

Hospital, Michigan, MI, U.S.A.Late cornified envelope (LCE) genes, located in the epidermal

differentiation complex on chromosome 1, encode a family of

18 proteins of unknown function, whose expression is largely

restricted to the epidermis. Deletion of two members, LCE3B

and LCE3C (LCE3B/C-del), is a widely replicated psoriasis risk

factor that interacts with the major psoriasis-risk gene HLA-

C*06:02. Disease-associated genetic risk factors often involve

noncoding variants, which has precluded understanding of

their functional consequences in complex diseases. We aimed

to investigate the expression and function of the LCE proteins

to explain the biology that underlies the association between

LCE3B/C-del and psoriasis. We used cis-expression quantitative

trait locus analysis and functional assays of LCE proteins in

in vivo skin and three-dimensional epidermal models. RNA-seq

data from normal and psoriatic human skin revealed that

LCE3B/C-del was associated with a significant induction of

LCE3A, directly adjacent to LCE3B/C-del. This phenomenon was

most strongly present in normal skin, where the LCE3A gene

is silent when LCE3B and LCE3C are present. We confirmed

these findings in a three-dimensional epidermal equivalent

model using primary keratinocytes from LCE3B/C-del geno-

typed donors. Functional analysis did not support a role for

LCE proteins in epidermal barrier function, but revealed that

psoriasis-associated LCE3 proteins, and LCE3A in particular,

have defensin-like antimicrobial activity against a broad variety

of bacterial taxa at low micromolar concentrations. Our find-

ings identify a hitherto unknown biological function for LCE3

proteins and suggest a central role for LCE3A in epidermal

host defence and LCE3B/C-del-mediated psoriasis risk.

FC05Environmental antigens may trigger HLA-C*06:02-mediated autoimmunity in psoriasisY. Arakawa, A. Arakawa, S. Vural, A. Galinski,S. Vollmer and J. PrinzDepartment of Dermatology, Ludwig-Maximilian-University of Munich,

Munich, GermanyPsoriasis vulgaris is a human leucocyte antigen (HLA)-

C*06:02-associated T-cell-mediated autoimmune skin disease

that develops upon epidermal infiltration and activation of

CD8+ T cells. Environmental and lifestyle factors may trigger

disease onset, and account for approximately 30% of disease

risk. Using a Va3S1/Vb13S1 T cell receptor (TCR) from a

pathogenic epidermal psoriatic CD8+ T-cell clone we have

recently shown that in psoriasis HLA-C*06:02 mediates an

autoimmune response against melanocytes, and we had identi-

fied a peptide from ADAMTS-like protein 5 as a melanocytic

antigen. In this study, we aim to identify environmental fac-

tors at the molecular level that translate the genetic predisposi-

tion into disease manifestation. TCRs are polyspecific. They do

not recognize specific antigens but react against HLA-presented

peptides sharing a particular amino acid pattern specific to this

TCR. After defining the amino acid pattern recognized by the

Va3S1/Vb13S1 TCR in the context of HLA-C*06:02 by pep-

tide library screening we searched environmental proteomes

for peptides sharing this particular pattern. Environmental can-

didate epitopes were tested for their ability to ligate the

ADAMTSL5-reactive Va3S1/Vb13S1 TCR when presented by

HLA-C*06:02. This way we identified a variety of peptides

contained in proteins from human skin and gut microbiomes,

from infectious pathogens including Chlamydia trachomatis, and

from foods (wheat, coffee, apple and spinach) that ligated the

Va3S1/Vb13S1 TCR. These results provide the first evidence

of environmental antigens that may serve as potential triggers

of the melanocyte-specific autoimmune response in psoriasis.

They suggest that exposure to environmental antigens may

drive priming and expansion of potentially self-reactive T cells

and thus initiate autoimmune disease responses. Through the

unbiased analysis of a pathogenic psoriatic TCR our data fur-

thermore may have important implications in understanding

© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)

2 Psoriasis Gene to Clinic



from gene to clinic

61ABSTRACTS

how environmental factors affect the risk for autoimmune dis-

eases in general.

FC06Analysis of psoriasis host-microbiome interactionsusing a universal transcriptomic approachT. Furnholm, M. Foo, J. Henderson, K. Shedden andA. JohnstonUniversity of Michigan, Ann Arbor, MI, U.S.A.Perturbations in host–microbe interactions may underlie the

triggering and worsening of psoriasis. 16S DNA sequencing

has indicated that psoriatic skin and tonsils have markedly

altered microbiomes; however, this method identifies bacteria

poorly and does not inform about altered microbial function.

The use of next-generation RNA sequencing (RNA-seq) to

study the actively transcribed genes from a microbial commu-

nity is currently hindered because existing alignment software

was designed for single-organism analysis. Thus, we devel-

oped new RNA-seq alignment software, Muscato, specifically

designed to carry out multigenome sequence alignment. Mus-

cato aligns hundreds of millions of RNA-seq reads to hundreds

of millions of genes in reasonable time frames and needs only

modest computational resources. When coupled to a func-

tional and taxonomic annotated gene database it allows simul-

taneous analysis of host and microbe gene expression. To

identify host–microbe interactions that may drive psoriasis,

we performed RNA-seq analysis on lesional skin (LS, n = 11),

nonlesional skin (NLS, n = 10) and tonsils (PT, n = 11) of

patients with psoriasis and normal controls (NS, NT n = 7). In

LS, 799 differentially expressed (more than twofold) human

genes mapped to KEGG functions including inflammation

(IL1B, IL8, NFKB1, TLR4), keratinocyte proliferation (EGF,

STAT3, CCND1, MYC), vascularization (VEGF, TEK, ANGPT1),

and T-cell responses (TGFB1, ITGB2, ICAM1, SGK1). This was

accompanied by reduced microbial diversity (Shannon Index:

LS 7.2, NLS 8.6, NS 8.3), with decreased Propionibacterium and

more than fourfold increased Streptococcus pyogenes colonization.

Nine of 64 (LS) and 40 of 90 (PT) streptococcal species were

more than twofold more abundant than in controls, with

S. anginosus and S. parasanguinis predominant. Multiple streptococ-

cal species had differentially expressed (more than fivefold)

virulence factors, including sialidase (NEU1, PT) streptolysin O

(Slo, LS), haemolysin (HlyC, PT and LS), exfoliative toxin (EtaA,

PT and LS), antimicrobial peptide resistance (DltA-D, PT and

LS), sec- and Type IV protein secretion systems and secreted

proteases, which may drive T-cell skin homing and activation.

Psoriasis tonsils yielded 333 other differentially abundant

microbial taxa, including Tannerella forsythia, Bulleidia extructa

W1219, Dialister invisus, Gemella sanguinis and Staphylococcus sciuri,

already implicated in inflammatory diseases (arthritis, endo-

carditis, atherosclerosis, periodontitis). Our novel RNA-seq

pipeline revealed enriched streptococcal superantigens in pso-

riatic skin and tonsils, together with species-level identification

of streptococci and other invasive bacteria that could drive

psoriasis and its comorbidities.

FC07Genetic variation contributes to response tobiologics: initial findings of the PsoriasisStratification to Optimise Relevant Therapy(PSORT) consortiumN. Dand on behalf of the PSORT consortiumKing’s College London, London, U.K.Biological therapies, which target specific components of key

proinflammatory immune pathways, can be highly effective in

the treatment of moderate-to-severe psoriasis. However, fail-

ure to respond carries a high cost, both economically and in

terms of patient care. The PSORT consortium therefore aims

to identify predictors of treatment response in psoriasis

patients. To date we have genotyped 3320 patients enrolled in

the British Association of Dermatologists Biologic Interventions

Register (BADBIR) using the Illumina OmniExpressExome

BeadChip. We further imputed human leucocyte antigen

(HLA) status for key alleles, including HLA-C*06:02, using

SNP2HLA software. For all patients the BADBIR register

includes detailed records of treatments, Psoriasis Area and

Severity Index (PASI) disease severity scores, and additional

demographic and clinical measurements. In an initial cohort

of 2467 patients we examined associations with biological

response reported in previous candidate variant studies. These

investigations have focused on genes implicated in psoriasis

susceptibility, biological response in other diseases, or drug

target pathways, but are yet to form a clear picture of how

genetic variants contribute to treatment response. For anti-

tumour necrosis factor (anti-TNF) (adalimumab, etanercept

and infliximab) and anti-interleukin (IL)-12/23 (ustek-

inumab) drugs we tested these variants for association with

response in patients with severe disease (baseline PASI > 10).

Response was defined at 3, 6 and 12 months as a 50%, 75%,

90% or 100% reduction in PASI relative to baseline. We found

modest evidence to support opposing roles for HLA-C*06:02under the two mechanisms of action, with presence of the

allele being positively associated with early response to ustek-

inumab (PASI 75 and 90 at 3 months; P < 0.01) but nega-

tively associated with excellent longer-term response to anti-

TNF agents (PASI 90 and 100 at 12 months, P < 0.01). We

also validate findings that link biological response with estab-

lished psoriasis susceptibility loci, such as TRAF3IP2 in the IL-

17 signalling pathway (adalimumab) and the LCE3B and LCE3C

genes within the epidermal differentiation complex (anti-

TNFs). However, our initial genome-wide results indicate the

presence of previously unreported genetic loci that display

stronger association with biological response. As our unique

datasets continue to accrue we expect our statistical power to

allow identification of novel genetic associations to improve.

We will subsequently examine in detail the interplay between

genetics and patient-specific clinical and demographic factors,

with the aim of predicting response and stratifying patients

according to their most likely effective biologic.

© 2017 British Association of Dermatologists British Journal of Dermatology (2017)

Psoriasis Gene to Clinic 3

FC08Comparative evaluation of cellular and molecularchanges associated with response to selectiveinterleukin (IL)-23 blockade vs. dual IL-12/23blockade in psoriasis skinK. Li,1 K. Campbell,1 S. Garcet,2 C. Brodmerkel1 andJ. Krueger2

1Janssen Research & Development, LLC, Spring House, PA, U.S.A.,2Laboratory for Investigative Dermatology, The Rockefeller University, New

York, NY, U.S.A.Emerging clinical data indicate that selective blockade of inter-

leukin (IL)-23 can achieve greater efficacy than dual blockade

of IL-12/23 in patients with moderate-to-severe psoriasis.

Ustekinumab targets the p40 subunit common to IL-12 and

IL-23, whereas guselkumab specifically targets the IL-23-speci-

fic p19 subunit. While differences in antibody potency may

explain therapeutic differences between ustekinumab and

guselkumab, we explored cellular and molecular changes in

the skin of patients with psoriasis treated with ustekinumab

or guselkumab to understand the mechanism underlying

selective IL-23 p19 inhibition. Ustekinumab data were derived

from the ACCEPT study (NCT00454584, n = 85), in which

patients with psoriasis received either 45 mg or 90 mg of

ustekinumab at weeks 0 and 4, and guselkumab data were

from the phase I psoriasis study (NCT00925574, n = 24) that

tested single subcutaneous doses of guselkumab. Skin biopsies

were collected at baseline and weeks 1 and 12 post-treatment

from each study to evaluate (i) histological improvement via

epithelial thickness, T cells (CD3) and myeloid dendritic cell

(CD11c) counts and (ii) molecular response to drug via

microarray. Biopsies from healthy volunteers served as con-

trols. The guselkumab 100-mg and 300-mg groups were

combined to increase analytical power. The IC50 of each drug

was evaluated by cell-based bioassays. The two cohorts are

comparable in baseline demographics, disease characteristics,

skin histopathology, psoriasis lesional molecular expression

profiles and significantly enriched canonical pathways. Block-

ade of IL-23 with guselkumab resulted in a significantly

greater reduction in CD3 and CD11c counts in the skin at

week12 relative to baseline when compared with ustekinumab

blockade (> 90% vs. ~70%). In patients who achieved > 50%

improvement in PASI score, guselkumab (n = 9) showed a

larger impact on the psoriasis transcriptomic profile than

ustekinumab 90 mg (n = 12) by week 1 and greater enhance-

ment was achieved by week12. Guselkumab neutralized 74%

of the psoriasis disease profile by> 80%, while ustekinumab

resolved only 21% at week 12. Expression of psoriasis disease

markers such as defensin-beta 4A and lipocalin 2 were fully

resolved by guselkumab beyond the level observed in nonle-

sional skin of patients with psoriasis, while ustekinumab

resolved these markers by only 32% and 63%, respectively. In

vitro, guselkumab showed higher potency (2–14 fold) than

ustekinumab in inhibiting IL-23 activity, which may con-

tribute to stronger neutralization of psoriasis disease markers

by guselkumab. This comparative study demonstrates that

guselkumab inhibits psoriasis-associated pathology and

resolves the skin transcriptomic psoriasis disease profile more

strongly than ustekinumab.

FC09Functional immunophenotyping analysis revealsadalimumab-induced impairment of tumournecrosis factor signalling in lymphoid cells inpsoriasisR.A. EjarqueOn behalf of the PSORT Consortium, London, U.K.Biological treatments have revolutionized the treatment of pso-

riasis. However, up to 30% of patients fail to respond, there-

fore there is a need to identify biomarkers to help direct

personalized treatments. The Psoriasis Stratification to Optimise

Relevant Therapy (PSORT) consortium is aimed at better

understanding the determinants of response to biological ther-

apies and delivering a stratifier algorithm to guide psoriasis

management. In our functional immunophenotyping

approach, we hypothesize that monitoring key transcription

factors downstream of the cytokines being targeted by biologi-

cal treatments provides insights into disease pathogenesis, as

well as biomarkers of disease and response to treatment. Here,

we investigate adalimumab, a tumour necrosis factor (TNF)-

targeting biological agent widely used for the treatment of

psoriasis. We evaluated the nuclear translocation of nuclear

factor (NF)-jB in key immune cell subsets, using imaging

flow cytometry. Fresh blood obtained from patients with pso-

riasis (n = 20) before treatment (baseline) and at weeks 1, 4

and 12 after commencing treatment, was stimulated with

TNF, interleukin (IL)-17, TNF + IL-17 and lipopolysaccharide

(LPS) for 30 min, stained and analysed. NF-jB translocation

was quantified using Fisher’s discriminant ratio (Rd score). At

baseline NF-jB translocation was observed upon TNF stimula-

tion in T cells (Rd 1.21 � 0.10), skin homing CLA+ T cells

(1.12 � 0.08), natural killer (NK) cells (0.85 � 0.15), NKT

cells (1.11 � 0.21), dendritic cells (DCs) (0.80 � 0.08),

monocytes (0.81 � 0.12) and neutrophils (0.49 � 0.10);

and upon LPS stimulation in monocytes (0.98 � 0.17), DCs

(0.42 � 0.07) and neutrophils (0.44 � 0.11). In contrast,

IL-17 stimulation did not induce NF-jB translocation, or aug-

ment the TNF-induced signal in any cell subset. Following

adalimumab, TNF-induced NF-jB translocation was almost

completely inhibited at each time point in T cells, CLA+

T cells, NK cells and NKT cells (92%, 89%, 81% and 84%,

respectively, at week 1, P < 0.01), and to a much lesser extent

in DCs and neutrophils (55% and 29% at week 1, P < 0.05),

while there was no effect in monocytes. In contrast, LPS-

induced NF-jB translocation was not affected by adalimumab

in monocytes, neutrophils and DCs. Interestingly, inhibition

of TNF-induced NF-jB translocation did not correlate with

the midterm response to the treatment, defined as ≥ 75%

improvement in Psoriasis Area and Severity Index (PASI 75)

and relative PASI, at any of the time points tested. Taken

together, these data suggest that the TNF inhibition exerted by

adalimumab in psoriasis mainly affects cells of the lymphoid

lineage, although this mechanism does not seem responsible





from gene to clinic

63ABSTRACTS

for the clinical response to therapy. Further phenotypic and

functional analysis are ongoing to address the molecular

mechanisms underpinning the clinical response to adalimumab

and to identify biomarkers of response.

FC10The genetic basis for most patients with pustularskin disease remains elusiveU. Huffmeier,1 S. L€ohr,1 P. Schulz,2 A. K€orber,3

J.C. Prinz,4 K. Sch€akel,5 S. Philipp,6 K. Reich,7

H. St€ander,8 A. Jacobi,9 K. Kingo,10 S. Koks,11

S. Gerdes,12 T. Schill,13 K.G. Griewank,3 S. Frey,14

K. Steinz,12 S. Uebe,1 M. Sticherling,15 H. Sticht,16

P. Gkogkolou,17 V. Oji,17 D. Wilsmann-Theis18 andR. M€ossner131Human Genetics, FAU Erlangen-N€urnberg, Erlangen, Germany; 2Fachklinik

Bad Bentheim, Bad Bentheim, Germany; 3Department of Dermatology,

University Hospital, Essen, Germany; 4Department of Dermatology,

University Hospital, Munich, Germany; 5Department of Dermatology,

University Hospital, Heidelberg, Germany; 6Department of Dermatology,

University Hospital, Berlin, Germany; 7Dermatologikum, Hamburg,

Germany; 8Department of Dermatology, Klinikum, Dortmund, Germany;9Institute for Health Services Research in Dermatology and Nursing,

University Medical Center Hamburg-Eppendorf, Hamburg, Germany;10Department of Dermatology and 11Department of Pathophysiology,

University of Tartu, Tartu, Estonia; 12Department of Dermatology,

University Hospital, Kiel, Germany; 13Department of Dermatology, University

Hospital, G€ottingen, Germany; 14Department of Immunology and Medicine

and 15Department of Dermatology, University Hospital, Erlangen, Germany;16Bioinformatics, Department of Biochemistry, FAU Erlangen-N€urnberg,

Erlangen, Germany; 17Department of Dermatology, University Hospital,

M€unster, Germany and 18Department of Dermatology, University Hospital,

Bonn, GermanyRare variants in the genes IL36RN, CARD14 and AP1S3 have

been identified as causing or contributing to pustular skin dis-

eases, primarily generalized pustular psoriasis (GPP). To

understand better the disease relevance of these genes, we

screened our cohorts of patients with pustular skin diseases

[primarily GPP and palmoplantar pustular psoriasis (PPP)] for

coding changes in these three genes. Carriers of single

heterozygous IL36RN mutations were screened for a second

mutation in IL36RN. Coding exons of IL36RN, CARD14 and

AP1S3 were sequenced in 67 patients: 61 with GPP, two with

acute generalized exanthematous pustulosis and four with

acrodermatitis continua suppurativa Hallopeau. We screened

IL36RN and AP1S3 for intragenic copy-number variants, with

258 patients with PPP screened for coding changes in AP1S3.

Eleven heterozygous IL36RN mutations carriers were analysed

for a second noncoding IL36RN mutation. Genotype–pheno-type correlations in carriers and noncarriers of IL36RN muta-

tions were assessed within the GPP cohort. The majority of

patients (GPP, 64%) did not carry rare variants in any of the

three genes. Biallelic and monoallelic IL36RN mutations were

identified in 15 and five patients with GPP, respectively. Non-

coding rare IL36RN variants were not identified in hetero-

zygous carriers. The only significant genotype–phenotype

correlation observed for IL36RN mutation carriers was early

age of disease onset. Additional rare CARD14 or AP1S3 variants

were identified in 15% of IL36RN mutations carriers. The iden-

tification of IL36RN mutation carriers harbouring additional

rare variants in CARD14 or AP1S3 indicates a more complex

mode of inheritance in pustular psoriasis. Our results suggest

additional disease-causing genetic factors in heterozygous

IL36RN mutation carriers outside IL36RN.

FC11ADAM17 and TIMP3 are psoriasis-relevantcheckpoints controlling T helper 17 programmingby inflammatory dermal dendritic cellsA. Kunze,1 A. Rendon,1 S. Oehrl,1 G. Murphy,2

A. Enk1 and K. Schakel1

1Department of Dermatology, Heidelberg, Germany and 2Cancer Research

U.K. Cambridge Institute, Cambridge, U.K.Psoriasis is a chronic inflammatory skin disease in which acti-

vated 6-sulfo-LacNAc-expressing (slan) dendritic cells

(slanDCs) function as inflammatory dermal dendritic cells

(DCs). slanDCs have a high interleukin (IL)-23-, IL-12-, IL-

1b- and tumour necrosis factor-a- producing capacity and

thereby programme T helper (Th)17/Th1-dominated T-cell

responses. Recently, an imbalance of expression of ADAM17

expression and its inhibitor tissue inhibitor of metallopro-

teinases (TIMP)3 was found in the epidermal compartment in

psoriasis, and restoration of TIMP3 levels induced regression

of skin lesions. We here examined the functional relevance of

ADAM17 for inflammatory dermal DCs in psoriasis. We

demonstrate by immunofluorescent staining and polymerase

chain reaction a downregulation of the endogenous ADAM17

inhibitor TIMP3 in both the dermis and the epidermis.

slanDCs but not CD1c+ DCs or CD141+ DCs were found to

express cell-surface ADAM17 as revealed by flow cytometry.

Furthermore, the enzymatic activity of ADAM17 on slanDCs

could be demonstrated by a specific fluorescence peptide

assay. Addition of the endogenous protease inhibitor TIMP3 to

slanDCs inhibited ADAM17 activation, and, most interestingly,

it blocked lipopolysaccharide-induced IL-23 and IL-12 produc-

tion by 60–70%; identical results were obtained with a highly

specific ADAM17-blocking antibody D1A12. To investigate the

biological relevance of these findings in the context of psoria-

sis, we set up cocultures of CD4+ T cells from patients with

psoriasis stimulated with allogeneic slanDCs in the presence of

the specific ADAM17-blocking antibody D1A12. A restimula-

tion of these cultures after 7 days revealed a largely reduced

IL-17 production of T cells, which was identical to the effects

achieved with an IL-12/IL23p40-specific antibody. In conclu-

sion, we identified the protease inhibitor TIMP3 as having

profound ADAM17-dependent immunoregulatory effects at

the level of inflammatory dermal DCs.



FC12Genotype and phenotype analyses revealed novelsusceptibility genes and new clinical classificationfor psoriasisB.-J. Feng,1,2 S. McCarthy,3 H. Li,2 K. Praveen,3

J. Walsh,4 J. Hawkes,1 M. Milliken,1 D. Goldgar,1,2

J. Reid,3 J. Overton,3 F. Dewey,3 C. Gonzaga-Jauregui,3 S. Guthery,5 K. Callis Duffin1 andG. Krueger11Department of Dermatology, 2Huntsman Cancer Institute, 4Department of

Rheumatology and 5Department of Pediatrics, University of Utah, Salt Lake

City, UT, U.S.A. and 3Regeneron Genetics Center, Regeneron Pharmaceuticals

Inc., Tarrytown, NY, U.S.A.Psoriasis is a complex multigenic disorder, with heritability

estimated to be 60–90%. Although several large-scale gen-

ome-wide association studies and linkage studies have been

performed, there is still a large proportion of the familial

relative risk not explained by the known loci. To search for

the missing heritability of psoriasis, we performed whole-

exome sequencing and array genotyping of 1133 patients

with psoriasis and 1176 healthy controls. Among the cases

of psoriasis there were 73 pedigrees ascertained through a

genealogy database of 8 million individuals with up to 12-

generation pedigrees. We jointly analysed the pedigrees and

case–control samples by the framework PERCH, which quan-

titatively integrates the deleteriousness of variants, quality of

variant calls, cosegregation of variants with disease within

pedigrees, association of variants with disease among cases

or controls, and the connection of each gene with known

psoriasis genes within a gene–gene interaction network. The

results demonstrated several candidate genes for psoriasis,

but none of them reached genome-wide significance. To cre-

ate a homogeneous subset of samples, we then performed a

latent class analysis to identify groups of patients with simi-

lar clinical phenotypes. This analysis yielded three classes.

Class 3 was associated with a younger age of psoriasis initia-

tion, more severe disease, and trauma- or injury-associated

disease onset or worsening. Familial risk analysis further

showed that this class of patients had the highest level of

familial aggregation. Our second round of genomic analysis

restricted to this group of patients resulted in the identifica-

tion of ADAMTS9 with genome-wide significance

(P = 8 9 10�7), a locus that was previously reported to

have a higher deletion rate in psoriatic arthritis than in

healthy controls. Class 2 psoriasis showed a moderate familial

clustering and is not sensitive to sunlight treatment. Pedi-

gree-informed genomic analyses identified novel candidate

genes segregating in families. Network analysis further sug-

gested a role for some candidate genes in epithelial immune

response. These results highlight the importance of pheno-

typic classification of cases in a complex disease and the pos-

sibility that new susceptibility loci for psoriasis can be

discovered using a combination of family-based and cohort

approaches such as PERCH. They also suggest a new classifi-

cation scheme for psoriasis that is relevant to disease aetiol-

ogy and clinical management. The whole-exome sequencing

and array genotyping of psoriasis cases and healthy controls

were funded and performed by Regeneron Pharmaceuticals

Inc., Tarrytown, NY, U.S.A.

FC13Advances in genomic studies of psoriasis in ChinaX. Zhang1,21Institute of Dermatology, Anhui Medical University, Hefei, China and2Institute of Dermatology, Fudan University, Shanghai, ChinaPsoriasis is a complex polygenic disease caused by a number

of susceptibility genes. We have been engaged in the genetic

research of psoriasis. Here we consider our studies and review

the significant progress in genomic research into psoriasis in

China. In 2002 we performed a genome-wide scan in 61 mul-

tiplex families showing that chromosomes 6p21 (PSORS1) and

4q31 may contain genes involved in the susceptibility to pso-

riasis vulgaris in the Chinese Han population. The OMIM data-

base included 4q31-q34, named as PSORS9. In the following

study, human leucocyte antigen (HLA)-C was identified as the

susceptibility gene within the PSORS1 locus by fine mapping

and association analysis. In 2009 we reported the first gen-

ome-wide association study (GWAS) in 6860 cases and 8472

controls in the Chinese population; we identified a new sus-

ceptibility locus for psoriasis within the late cornified envelope

gene cluster. Subsequently, we extended our GWAS with a

multistage replication study in 11 425 cases and 17 107 con-

trols and identified six new susceptibility loci. In addition, we

presented the largest transethnic genome-wide meta-analysis

of psoriasis in 15 369 cases and 19 517 controls and identi-

fied four novel associations with psoriasis. In 2010 we coop-

erated with the Beijing Genomics Institute and first carried out

exome sequencing and targeted sequencing of psoriasis in

10 727 cases and 10 528 controls. Seven common and low-

frequency nonsynonymous single-nucleotide variants were

identified within known psoriasis susceptibility genes that

were associated with psoriasis risk. In order to investigate the

coding variants in psoriasis systematically, an exome-wide

association study in 42 760 individuals was first carried out

using exome array in 2015. Sixteen coding variants were sig-

nificantly associated with psoriasis, and these findings high-

light the genetic contributions of common coding variants to

the pathogenesis of psoriasis. In 2016 we carried out a com-

prehensive analysis of genetic variation in the major histocom-

patibility complex (MHC) region by directly sequencing the

whole region in 20 635 individuals of Han Chinese ancestry

and constructed a reference panel of the MHC variants (Han-

MHC database) for imputation. We further identified multiple

independent new susceptibility loci in HLA-C, HLA-B, HLA-

DPB1, BTNL2 and rs118179173 associated with psoriasis. We

performed a three-stage epigenome-wide association study in

262 skin and 48 peripheral blood mononuclear cell samples.

This study not only revealed genome-wide methylation pat-

terns for psoriasis but also identified strong associations

between the skin-specific DNA methylation of nine disease-

associated differentially methylated sites and psoriasis. Based





from gene to clinic

65ABSTRACTS

on 15 years of hard work, there have been great advances and

tremendous achievements in genetic research of psoriasis in

Chinese Han population. So far, more than 40 robust suscepti-

bility loci have been identified and confirmed to be associated

with psoriasis in the Chinese Han population. These genetic

loci may help to build the foundation for genetic diagnosis

and personalized treatment for patients with psoriasis in the

near future. However, substantial additional studies, including

functional and gene-targeted studies, are required to confirm

the causality of the genetic variants and their biological rele-

vance in psoriasis development.

FC14iRhom2: a mechanistic hub in keratinocytehyperproliferation and psoriasis?M. Brooke,1 T. Maruthappu,2 A. Chikh1 andD. Kelsell11Blizard Institute, Barts & The London School of Medicine & Dentistry,

London, U.K. and 2St John’s Institute of Dermatology, Guy’s and St Thomas’

NHS Trust, London, U.K.iRhom2 is a proteolytically inactive member of the rhomboid

family of intramembrane proteases, with recently emerging

key functions in epidermal homeostasis. We and others have

shown that iRhom2 mediates the maturation of the broad-

spectrum sheddase enzyme ADAM17, the protease solely

responsible for the cleavage and release of soluble cytokines

including tumour necrosis factor (TNF)-a and multiple

ligands of epidermal growth factor receptor (EGFR; including

amphiregulin and TGF-a). Subsequently, we have also

described a unique role for iRhom2 as a key regulator of the

hyperproliferation-associated keratin 16. The enormous suc-

cess of TNF-a inhibition in psoriasis treatment, in addition to

the established role of iRhom2/ADAM17 substrates in the

development of psoriatic plaques, and the upregulation of ker-

atin 16 in lesional psoriatic skin, therefore point to a hitherto

unidentified role for iRhom2 in psoriasis. In support of this,

we have shown that gain-of-function iRhom2 mutations result

in elevated shedding of TNF-a and EGFR ligands, hyperactive

EGFR signalling and keratin 16 upregulation, features of an

aberrant wound healing phenotype and hyperproliferative epi-

dermis. Conversely, although Irhom2 knockout mice appear

phenotypically normal at birth and in adulthood, we have

found that they develop significantly thinner paw epidermis

relative to controls, with barely detectable keratin 16 expres-

sion. Matching these data, we have shown that short hairpin

hRNA knockdown of iRhom2 in hyperproliferative ker-

atinocytes placed in three-dimensional organotypic culture

results in the generation of thinner epidermal equivalents.

Additionally, it has been shown that the Irhom2 knockout

mouse exhibits reduced inflammatory responses to infectious

stimuli and appears to be protected from developing another

TNF-a-driven disease, rheumatoid arthritis, in a transgenic

model. We have identified that iRhom2, ADAM17, TNF-a and

EGFR ligands are significantly upregulated at the mRNA level

in lesional psoriatic epidermis relative to nonlesional skin.

Intriguingly, we have also observed by immunofluorescence

that iRhom2 localization in human lesional psoriasis skin dif-

fers from that of controls. iRhom1, a relative of iRhom2, is

also capable of regulating ADAM17, but incapable of keratin

16 regulation. However, iRhom1 appears to regulate a low

level of ADAM17 activity in basal keratinocytes only, and

unlike iRhom2 it is not upregulated in lesional psoriasis. As a

consequence, therapeutic targeting of iRhom2 would allow

for the inhibition of excessive, disease-associated ADAM17-

dependent shedding, without affecting the relatively lower

iRhom1-dependent activity important for normal skin home-

ostasis. Therefore, as psoriasis shares several disease mecha-

nisms with those seen as consequences of iRhom2

hyperactivity, targeting iRhom2 in psoriasis represents an

attractive strategy.

FC15Identifying chromatin interactions betweenpsoriasis-associated variants and target genesusing Capture Hi-CH. Ray-Jones,1,2 A. McGovern,1 P. Martin,1 K. Duffus,1

S. Eyre1 and R.B. Warren1,2

1University of Manchester, Manchester, U.K. and 2Salford Royal NHS

Foundation Trust, Manchester, U.KGenome-wide association studies (GWASs) have identified

many risk loci for psoriasis, but most lead variants are outside

of protein-coding regions and therefore have an unknown

function. It is hypothesized that these variants regulate gene

function through DNA looping, whereby the variant is

brought into close contact with a distant gene promoter. To

identify putative gene targets, Capture Hi-C (CHi-C) can be

utilized. It is a cutting-edge chromosome conformation cap-

ture method that gives an unbiased view of chromatin interac-

tions in targeted regions of the genome. This work applied

CHi-C in psoriasis risk loci using relevant cell types and condi-

tions. CHi-C libraries were generated in duplicate using rele-

vant cell lines: MyLa (CD8+ T cells) and HaCaT

(keratinocytes). Two libraries were also generated from HaCaT

cells stimulated with interferon IFN)-c. RNA capture baits

were designed to target all known psoriasis-associated GWAS

loci; each locus was defined by a set of variants in linkage dis-

equilibrium with the lead GWAS variant (r2 > 0.8). The

libraries underwent next-generation sequencing generating

75-bp paired ends. The sequences were analysed using the

bioinformatics pipelines HiCUP and CHiCAGO. Chromatin

interaction data were obtained for psoriasis risk loci across the

genome represented by 107 lead GWAS variants (59 in Euro-

pean cohorts, 42 in Chinese and four in both populations).

There were 13 393, 6737 and 6956 significant interactions in

MyLa, unstimulated HaCaT and stimulated HaCaT cells, respec-

tively (CHiCAGO score > 5). In approximately 25% of cases,

the interactions overlapped with gene promoter regions

defined by fragments within 500 bp of a transcription start

site, corresponding to 1075 genes and noncoding RNAs in

total. This implicated gene targets in several loci; for example

NFKBIZ in 3q12.3 and KLF4 in 9q31.2. In some loci, the

potential target gene was narrowed down from a list of



compelling candidates. For example, the 1p36.23 locus har-

bours several likely genes including TNFRSF9, ERRFI1 and

SLC45A1. In HaCaT cells the psoriasis-associated variation inter-

acted with the promoter of ERRFI1, a gene encoding a protein

that inhibits epidermal growth factor receptor signalling and

is thought to be required for normal keratinocyte prolifera-

tion. In conclusion, this is the first use of CHi-C across all

psoriasis risk loci, demonstrating how intergenic variation

may contribute towards the pathogenicity of psoriasis. The tar-

get genes identified in these loci are candidates for down-

stream functional investigation as potential therapeutic targets

in psoriasis.

FC16The psoriasis-associated Act1(D10N) variantreduces responses to interleukin-17 but enhancesT helper 17 responses to polyclonal activationS. Lambert,1 C. Hambro,1 A. Johnston,1 R. Nair1 andJ. Elder1,21University of Michigan, Ann Arbor, MI, U.S.A. and 2Ann Arbor VA

Hospital, Ann Arbor, MI, U.S.A.Act1/TRAF3IP2 links the interleukin (IL)-17 receptor to down-

stream pathways. The TRAF3IP2 gene resides in a psoriasis sus-

ceptibility locus, with the single-nucleotide polymorphism

rs33980500, D>N in position 10 of Act1 increasing risk. In

order to investigate the effect of the Act1 D10N variant on IL-

17 signalling, we isolated keratinocytes, fibroblasts and

peripheral blood mononuclear cells (PBMCs) from individuals

homozygous for the common allele (wild-type, n = 9) or the

risk variant (D10N, n = 5). We found that both keratinocytes

and fibroblasts from Act1 D10N homozygotes displayed atten-

uated responses to IL-17 stimulation. Upon IL-17 stimulation

(100 ng mL�1, 3 h), fibroblasts from Act1 D10N homozy-

gotes had reduced mRNA expression of IL1A (46.4 � 3.6% of

wild-type, P = 0.04) and CCL7 (33.2 � 4.8% of wild-type,

P = 0.01). Keratinocytes from Act1 D10N homozygotes had

lower mRNA induction of CCL20 (20.9 � 4.4% of wild-type,

P = 0.04), DEFB4 (47.5 � 27% of wild-type, P = 0.013), and

IL36G (36 � 7.6% of wild-type, P = 0.023). We induced T

helper (Th)17 differentiation by CD3/CD28 bead stimulation

of PBMCs for 7 days in the presence or absence of neutrophil

extracellular traps (NETs), with further activation by phorbol

myristate acetate and ionomycin (P/I) for the final 6 h or

24 h. Under these conditions, we found that Ac1 D10N

homozygotes were significantly more responsive than wild-

type cells, with a fivefold increase in IL-17 elaboration by

enzyme-linked immunosorbent assay (19.1 � 3.7 ng mL�1

vs. 3.4 � 1.9 after 24 h of P/I treatment; n = 2). Act1 D10N

homozygotes also manifested increased IL-17A and IL-17F

mRNAs (3.2 and 3.5-fold vs. wild-type, respectively, after 6 h

of P/I treatment). Notably, these differences were observed

only in the presence of NETs. These results suggest that

despite reducing target cell responses to IL-17 stimulation, the

psoriasis-associated Act1 D10N variant increases Th17 differ-

entiation and/or responsiveness to polyclonal stimulation,

consistently with the genetic evidence implicating it as a pso-

riasis risk variant.

FC17ERAP1 risk variants in psoriasis vulgaris affectautoantigen presentationA. Arakawa,1 S. Vollmer,1 E. Reeves,2 E. James2 andJ.C. Prinz11Ludwig-Maximilians-University, M€unich, Germany and 2Southampton

General Hospital, Southampton, U.K.Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims the

NH2-terminus of antigenic peptide precursors to the appropri-

ate length for binding to and presentation by human leucocyte

antigen (HLA)-class I molecules to the T-cell antigen receptors

(TCRs) of T cells. ERAP1 polymorphisms result in different

peptide trimming specificities and activities. In various

autoimmune diseases ERAP1 variants display gene–gene inter-

actions with the predisposing HLA class I risk alleles. Psoriasis

vulgaris is an HLA-C*06:02-associated autoimmune disease. In

psoriasis, HLA-C*06:02 mediates an autoimmune response

against melanocytes through autoantigen presentation. Epistasis

between HLA-C*06:02 and ERAP1 variants affects the risk for

psoriasis, but the mechanisms of this gene interaction

remained unknown. We have used an HLA-C*06:02-presentedmelanocyte autoantigen, ADAMTS-like protein 5 (ADAMTSL5),

and an ADAMTSL5-specific Va3S1/Vb13S1 TCR from patho-

genic psoriatic CD8+ T cells to determine the role of ERAP1

variants in disease risk. Our data show that ERAP1 variants

increasing psoriasis risk were highly effective in generating

the antigenic ADAMTSL5 peptide from NH2-terminally elon-

gated ADAMTSL5 peptide precursors. Instead, a protective

ERAP1 variant reduced the availability of the antigenic

ADAMTSL5 peptide presumably through overtrimming and

peptide destruction. Several other peptide ligands from natural

human proteins that were recognized by the Va3S1/Vb13S1TCR due to TCR polyspecificity were not processed from pep-

tide precursors into antigenic peptides of appropriate length

for HLA binding and presentation. Thus, using a proven psori-

atic autoantigen from melanocytes and a pathogenic psoriatic

TCR, these experiments provide direct evidence of how differ-

ent ERAP1 variants can affect the risk of autoimmunity in pso-

riasis through differential trimming of a peptide autoantigen.

They furthermore demonstrate that the potential antigenicity

of self-peptides depends on ERAP1 trimming and indicate that

different ERAP1 affinities for different amino acid sequences

of precursor peptides finally determine autoantigens in CD8+

T-cell-mediated autoimmune diseases.

FC18Tumour necrosis factor blockade induces adysregulated type I interferon response withoutautoimmunity in paradoxical psoriasisC. Conrad,1 J. Di Domizio,1 A. Mylonas,1 O. Demaria,1

C. Belkhodja,1 A. Navarini,2 A.-K. Lapointe,1

L. French,2 M. Vernez1 and M. Gillliet1





from gene to clinic

67ABSTRACTS

1Department of Dermatology, University Hospital CHUV, Lausanne,

Switzerland and 2Department of Dermatology, University Hospital of Zurich,

Zurich, SwitzerlandAntitumour necrosis factor (anti-TNF) agents are highly effec-

tive in the treatment of psoriasis. However, in 2–5% of treated

patients they induce psoriasis-like skin lesions called paradoxi-

cal psoriasis. The pathogenesis of this side-effect and its dis-

tinction from classical psoriasis remain largely unknown. Here

we performed a comprehensive clinical, histological and gene

expression analysis of skin lesions from 25 patients with para-

doxical psoriasis. Paradoxical psoriasis is characterized by a

selective, uniform increase in type I interferon expression and

plasmacytoid dendritic cell (pDC) accumulation, despite

marked clinical and histological variations. Anti-TNF agents

stimulates pDCs to produce exaggerated levels of type I inter-

feron by inhibiting TNF-mediated pDC maturation both in vitro

and in a skin injury mouse model. Via type I interferon,

anti-TNF agents induce a psoriatic skin phenotype reflecting

paradoxical psoriasis, which is, unlike classical psoriasis, inde-

pendent of T cells. These findings indicate that paradoxical

psoriasis represents an overactive innate inflammation driven

by pDC-derived type I interferon; however, this is self-con-

tained as it does not lead to T-cell autoimmunity.

FC19Activation of resident T cells in resolved psoriasisreveals tissue responses that stratify clinicaloutcomeI.G. Serezal, C. Classon, S. Nyl�en, N.X. Land�en,E. Martini, S. Cheuk and L. EidsmoKarolinska Institutet, Stockholm, SwedenPathological resident memory T (TRM) cells poised towards

interleukin (IL)-17 production are enriched in resolved psoria-

sis, a focal inflammatory disease that often relapses in fixed

sites of the skin. To investigate the impact of resident T cells

on their immediate microenvironment, skin explants were

stimulated ex vivo with OKT-3, a CD3-activating antibody.

Transcriptomic analyses with RNA sequencing and Nanostring

revealed that T-cell activation resulted in upregulation of the

interferon-c-induced chemokine genes CXCL10 and CXCL9 in

healthy, active and resolved psoriasis. In contrast, IL-17-related

DEFB2 and genes involved in keratinocyte differentiation

(SPRR2 family) were selectively induced in both active and

resolved psoriasis, indicating that pathogenic TRM cells affect

tissue homeostasis in resolved psoriasis. An integrative analysis

of the response patterns to T-cell activation highlighted that

the balance between IL17 or DEFB2 and CXCL10 correlated to

the time to clinical relapse in patients after ultraviolet B treat-

ment, at both the RNA and protein levels. Our data show that

skin T cells induce clinically relevant tissue responses, with

the potential locally to steer focal pathology in psoriasis. Strati-

fication of such responses may be used to predict disease out-

come in resolved psoriatic skin.

FC20Longitudinal follow-up of arterial structure andfunction in patients with severe psoriasis treatedby anti-interleukin (IL)-12/IL-23 agents comparedwith tumour necrosis factor inhibitorsM. Viguier,1 H. Khettab,2 I. Hamdidouche,2

P. Boutouyrie2 and H. Bachelez31Dermatology Department, CHU Robert Debr�e, Reims, France; 2Pharmacology

department, Hopital Europ�een Georges Pompidou, INSERM U970, Paris,

France and 3Dermatology Department, Hopital Saint-Louis, INSERM UMR

1163, Institut Imagine, Paris, FrancePatients with chronic severe plaque psoriasis are at increased

cardiovascular risk. As the respective impacts of biological

therapy for psoriasis with TNF inhibitors (TNFis) and anti-

interleukin (IL)-12/IL-23 agents (ustekinumab) on cardiovas-

cular atherosclerotic disease are still debated, we launched a

single-centre parallel-group study aiming to characterize large

artery remodelling and stiffness during longitudinal follow-up

under any of the three approved TNFis (adalimumab, etaner-

cept, infliximab) and anti-IL-12/23. For this, we consecutively

included 31 patients with psoriasis starting treatment with

TNFis or anti-IL12/23 agents. Patients had to require systemic

biotherapies to control their psoriasis and have at least one

additional cardiovascular risk. Measurement of arterial struc-

ture and function was assessed blindly with respect to biolog-

ics at baseline and during treatment. The assessed parameters

were the following: diameter, intima media thickness (IMT)

and stiffness of the two carotids (echotracking); carotid pulse

wave velocity (PWV), carotid-to-femoral PWV and central

pressure (applanation tonometry). These were analysed using

mixed models. Patients were treated with either a TNFi

(n = 13) or an anti-IL-12/23 agent (n = 18). The male-to-

female sex ratio was 1.2 and the mean age was 49.8 years;

87% were overweight or obese, 55% were smokers, 32% had

controlled arterial hypertension, 23% had a personal or family

history of cardiovascular events and 13% had diabetes. The

patients did not differ according to baseline characteristics,

except for more frequent statin use in the anti-IL12/23 group

(28% vs. 0%). The mean follow-up was 13 � 3 months with

a mean number of three measurements. Carotid diameter did

not change significantly during follow-up. IMT increased more

with anti-IL12/23 than TNFis (Δ + 75 lm, P = 0.10). Carotid

distension and carotid distensibility decreased significantly

under anti-IL12/23, whereas it increased with a TNFi, inde-

pendently of blood pressure (Δ �3.82 kPa, P < 0.035). Caro-

tid PWV and carotid-to-femoral PWV increased independently

of blood pressure with anti-IL12/23 and decreased with TNFi

(Δ +1.15 m s�1, P < 0.05; + 1.60 m s�1, P < 0.03, respec-

tively). The increased arterial stiffness and the hypertrophy of

large arteries during longitudinal follow-up of patients under

ustekinumab in comparison with those receiving TNFis sup-

port differential impacts of these two classes of biologics on

arterial remodelling. Whether this is due to a protective effect

of TNFis and/or opposite effect of anti-IL12/23 remains to be

determined.



FC21Real-world experience with apremilast in patientswith psoriasis: interim analysis of 104 patientsfrom the APPRECIATE studyE. Kleyn,1 M. Radtke,2 C. Bundy,3 K. Eyerich,4

M. St�ahle,5 M. Cordey,6 V. Koscielny,6

C.E.M. Griffiths7,8 and M. Augustin2

1The Dermatology Centre, The University of Manchester, Manchester, U.K.;2Institute for Health Services Research in Dermatology and Nursing,

University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3School

of Healthcare Sciences, University of Cardiff, Cardiff, U.K.; 4Department of

Dermatology and Allergy, Technical University of Munich, Munich,

Germany; 5Unit of Dermatology, Department of Medicine, Karolinska

Institutet, Stockholm, Sweden; 6Celgene International, Boudry, Switzerland;7The Dermatology Centre, Manchester, U.K. and 8The University of

Manchester, Manchester, U.K.Apremilast, an oral phosphodiesterase 4 inhibitor, is approved

for the treatment of adult patients with moderate-to-severe

plaque psoriasis and/or active psoriatic arthritis. This ongoing,

retrospective, cross-sectional combined study of patients with

psoriasis treated with apremilast, in a real-world setting, aims

to investigate patient characteristics, treatment outcomes and

benefits and limitations as perceived by patients and physicians

(NCT02740218). Presented here is a 6-month interim analysis

of results from 41 sites in Germany, Sweden and the U.K.

(42, 31 and 31 patients, respectively). Medical record review

(n = 104) showed that the patients’ mean age was 52.4 years

(median 53.0); 60 (57.7%) were female and mean time since

psoriasis diagnosis was 20.8 � 15.6 years. Common comor-

bidities included metabolic syndrome (22, 21.2%), psoriatic

arthritis (36, 34.6%) and obesity (11, 10.6%), and 91

(87.5%) had received at least one prior systemic or photother-

apy for psoriasis. At apremilast initiation, disease assessments

(mean � SD) included Psoriasis Area and Severity Index

(12.6 � 7.9), psoriasis-involved body surface area

(32.8 � 25.0%) and Dermatology Life Quality Index (DLQI)

score (12.8 � 7.3). For the Physician’s Global Assessment

(PGA) of disease activity, 69 patients (66.3%) had scores ≥ 3.

Reasons for initiating apremilast were ‘previous therapy was

ineffective’ (59.6%), ‘intolerant to previous therapy’ (26.0%),

‘contraindications to conventional therapies’ (7.7%) and

‘patient choice’ (3.9%). At 6 � 1 months’ follow-up, 74

(71.2%) patients continued to receive apremilast; 30 had dis-

continued due to lack of efficacy (n = 15, 14.4%), safety/tol-

erability (n = 11, 10.6%) or other reasons (n = 4, 3.9%).

Data available from patient charts showed that PASI 75 (≥75% reduction from baseline) was achieved by 20 of 52

patients (38%), 16 of 23 (70%) achieved ≥ 5-point improve-

ment on the DLQI, and 31 of 56 patients (55%) achieved a

PGA rating of 0 (clear) or 1 (almost clear). Based on these

assessments clinicians agreed or strongly agreed that apremilast

showed a rapid (62.5%) and sustained (54.8%) response, and

notably reduced plaque psoriasis (66.4%). Among patients

with the following symptoms at baseline, improvements were

reported with scalp (47 of 71, 66%), nail (24 of 42, 57%),

palmoplantar (18 of 26, 69%), nongenital inverse (20 of 28,

71%) and genital psoriasis (16 of 23, 70%), as well as pruri-

tus (49 of 67, 73%). Fifty patients (48.1%) reported at least

one adverse event. Adverse events were consistent with the

known safety profile of apremilast, including diarrhoea

(n = 20, 19.2%), nausea (n = 17, 16.3%) and headache

(n = 12, 11.5%). This interim analysis of a multinational real-

world study found meaningful improvements in physician-

assessed and patient-reported outcomes with apremilast ther-

apy in patients with psoriasis with a variety of disease mani-

festations and comorbidities. This study was funded by

Celgene Corporation.

FC22Topical methotrexate gold nanoparticles reduceimiquimod-induced inflammation in miceA. €Ozcan,1 D. Bunton,2 G. Macluskie,2 M. Duric,3

J. Barry3 and A. Kolios11University Hospital Zurich, Zurich, Switzerland; 2ReproCELL Europe Ltd,

Glasgow, U.K. and 3Midatech Pharma, Abingdon, U.K.Methotrexate (MTX) is a widely used immunosuppressive

agent for the treatment of several autoimmune and chronic

inflammatory conditions, such as rheumatoid arthritis and

psoriasis. MTX is usually administered systemically, which can

cause side-effects, including liver damage and kidney failure.

Due to its polarity and high molecular weight, topical MTX

penetrates very poorly through the skin barrier and therefore

needs a targeted drug delivery system to overcome biological

barriers. Gold nanoparticles (GNPs) have been used as a tar-

geted drug delivery system in cancer therapy and have

recently been shown to deliver MTX into the skin by topical

application. Here we explored the therapeutic potential of a

novel topical MTX formulation in inflammatory skin disease.

The skin permeability of MTX was increased via conjugation

to GNPs (MTX-GNP). Using the imiquimod-induced mouse

model of psoriasis, where imiquimod is applied on the ear of

a mouse, we evaluated the in vivo efficacy and functionality of

MTX-GNPs. Subcutaneous administration of MTX-GNPs ame-

liorated imiquimod-induced inflammation in a dose-depen-

dent manner, as measured by ear thickness, erythema and

scaling. Systemic MTX-GNP demonstrated a superior anti-

inflammatory action compared with systemic MTX on imiqui-

mod-induced inflammation. At day 5, the mean ear thickness

(MET) of the MTX-GNP treatment group was 286 lm,

whereas the MET of the MTX group was 335 lm. Compared

with the treatment group who received imiquimod only (MET

351 lm), the ear thickness of the MTX-GNP-treated mice was

significantly lower, but the effect of MTX alone was not

(P = 0.034 and P = 1.00, respectively). Additionally, MTX

treatment displayed higher toxicity than MTX-GNP. Topical

MTX-GNPs were formulated based on the systemic dose

inducing the highest clinical efficacy but the least toxicity.

Topical application of MTX-GNP gel significantly reduced imi-

quimod-induced inflammation on day 5, whereas a gel for-

mulation of MTX showed no improvement (MET of mice

treated with IMQ only: 390 lm; MET of MTX-GNP group:

288 lm, MET of MTX group: 346 lm; MTX-GNP vs.





from gene to clinic

69ABSTRACTS

imiquimod only: P = 0.0025, MTX vs. IMQ only P = 0.38).

GNPs significantly improve delivery of MTX to the skin, thus

allowing transdermal application of the drug. Topical MTX-

GNPs reduced imiquimod-induced inflammation in mice

without significant toxicity. MTX-GNPs should be considered

as a nonsteroidal therapeutic option for inflammatory skin

diseases.

FC23Efficacy and safety of secukinumab in patients whohave failed antitumour necrosis factor-a treatmentfrom the U.K. and Republic of Ireland: results ofthe SIGNATURE studyR.B. Warren,1,2 J. Barker,3 D. Burden,4 A. Finlay,5

C. Hatchard,6 P. Jeffery,6 R. Williams6 andC.E.M. Griffiths1,21University of Manchester, Manchester, U.K.; 2Royal Salford NHS Foundation

Trust, Manchester, U.K.; 3St John’s Institute of Dermatology, London, U.K.;4Royal Infirmary of Edinburgh, Edinburgh, U.K.; 5Cardiff University School

of Medicine, Cardiff, U.K. and 6Novartis Pharmaceuticals U.K. Ltd, Frimley,

U.K.Secukinumab, a human anti-interleukin-17A monoclonal anti-

body, has been shown to be efficacious in the treatment of

moderate-to-severe plaque psoriasis, with a sustained effect

and a favourable safety profile. This open-label, noncompara-

tor study was designed to investigate the safety and efficacy of

secukinumab (300 mg and 150 mg) in patients with active

moderate-to-severe, chronic plaque psoriasis who had a prior

efficacy failure on antitumour necrosis factor-a biological

therapy, as defined by the National Institute for Health and

Care Excellence (NICE) criteria, in the U.K. and Republic of

Ireland population. In total 235 adults with moderate-to-

severe chronic plaque psoriasis from 53 sites received secuk-

inumab as subcutaneous injections of 300 mg or 150 mg for

a 16-week initiation period (weeks 0–4, 8, 12 and 16) fol-

lowed by two maintenance periods up to 72 weeks. There

were three subgroups: (i) inadequate response to first anti-

TNF-a therapy; (ii) adequate response after first anti-TNF-atherapy but subsequent loss of efficacy and (iii) failed more

than one anti-TNF-a therapy due to inadequate response. The

primary end point was the percentage of patients achieving

≥75% reduction in Psoriasis Area and Severity Index (PASI 75)

at 16 weeks. Key secondary outcomes included PASI 90 at

16 weeks. Safety was comprehensively assessed throughout

the study. The response rate for PASI 75 was 65.3% for

300 mg (95% confidence interval 52.4–76.7, P < 0.001) and

44.3% for 150 mg (95% confidence interval 31.8–57.5,P < 0.001). There was a statistically significant proportion of

PASI 75 responders at 16 weeks in all three subgroups for

300 mg, vs. a null hypothesis of > 20% placebo response

expected; however, only subgroup (ii) achieved statistical sig-

nificance in the 150-mg group. A Bonferroni correction was

applied to the primary and seven key secondary end points

resulting in two-sided hypothesis testing at the 0.625% level

and 99.375% confidence intervals. The PASI 90 response rate

at 16 weeks for 300 mg was 41.5%.The majority of adverse

events were mild to moderate in severity. The most com-

monly reported adverse events during the initiation period in

the 300-mg group were nasopharyngitis (16.9%), headache

(15.3%), oropharyngeal pain (11.0%) and nausea (11.0%).

Candida infection was reported in 4.2% of patients in the 300-

mg group in the first 16 weeks of treatment. The results of

this study provide reassurance of the real-world safety and

efficacy of secukinumab in this hard-to-treat patient popula-

tion with prior anti-TNF-a failure. This study was sponsored

by Novartis.

FC24The genetic analysis of a large pustular psoriasisresource highlights differential effects for IL36RNand AP1S3 mutationsS. Twelves,1 K. Farkas,2 S.E. Choon,3 D. Burden,4

C.E.M. Griffiths,5 A. Irvine,6 E. Tan,7 M. Szell,2

Z. Bata-Csorgo,2 C. Smith,1 F. Capon1 and J. Barker1

1King’s College London, London, U.K.; 2University of Szeged, Szeged,

Hungary; 3Hospital Sultanah Aminah, Johor Bahru, Malaysia; 4Royal

Infirmary of Edinburgh, Edinburgh, U.K.; 5University of Manchester,

Manchester, U.K.; 6Our Lady’s Children’s Hospital, Dublin, Ireland and7National Skin Centre, Singapore, SingaporePustular psoriasis is a rare autoinflammatory skin disease char-

acterized by the appearance of small sterile pustules, resulting

from the accumulation of neutrophils in the epidermis. The

disease can be further classified into three subtypes. General-

ized pustular psoriasis (GPP) is an acute condition, manifest-

ing with flares of widespread pustulation that may be

accompanied by systemic inflammation. Acrodermatitis con-

tinua of Hallopeau (ACH) and palmoplantar pustular psoriasis

(PPP) are chronic and localized diseases affecting the nail

apparatus (ACH) or the palms and/or soles (PPP). Mutations

in IL36RN and AP1S3 have been associated with a proportion

of cases of pustular psoriasis, but the rarity of the disease has

hindered attempts to study correlations between genotype and

phenotype. Here we have sought to address this issue through

the analysis of 400 affected individuals (210 GPP, 17 ACH

and 173 PPP), representing the largest cohort examined to

date. We found AP1S3 mutations only in patients of European

descent, where they accounted for 10.6% (22 of 207) of cases

of pustular psoriasis. AP1S3 alleles did not vary in frequency

among the various disease subtypes (P = 0.13), but displayed

a significant sex bias as 21 of 22 (96%) AP1S3-positive cases

were female (P= 0.032). This suggests that the penetrance of

AP1S3 mutations is modified by sex-dependent factors. IL36RN

alleles showed a less marked sex bias, with women accounting

for only 62% (38 of 61) of mutation carriers. In contrast, we

found that mutation rates were higher in GPP (22.9%, 48 of

210) and ACH (18%, three of 17) compared with PPP (6.5%,

10 of 154, P < 0.001). In conclusion, our findings indicate

that IL36RN alleles are most strongly associated with GPP,

while AP1S3 mutations confer a broader risk of pustular psori-

asis. The data also highlight PPP as the disease subtype that is

least understood at the genetic level, demonstrating the need

for further gene identification work.



FC25Transcriptomic profiling of interleukin (IL)-36A,IL-36B and IL-36G cytokine responses inkeratinocytes demonstrates a high degree ofoverlap and dependency on MYD88 and nuclearfactor-kB signallingW. Swindell,1 M. Sarkar,1 M. Beamer,1 X. Xing,1

M. Kahlenberg,1 N. Ward,2 J. Voorhees,1 L. Tsoi,1

Y. Liang1 and J. Gudjonsson11University of Michigan, Ann Arbor, MI, U.S.A. and 2Case Western

University, Cleveland, OH, U.S.A.Interleukin (IL)-36 cytokines have recently emerged as key

proinflammatory cytokines in the pathogenesis of psoriasis,

particularly its pustular subtypes. However, little is known

about IL-36 downstream signalling and transcriptional

responses. The aim of this study was to elucidate transcrip-

tional responses downstream of the three IL-36 cytokines

(IL-36A, IL-36B and IL-36G) in keratinocytes using high-reso-

lution RNA sequencing. We identified between 788 and 1747

differentially expressed genes significantly altered by IL-1b, IL-36a, IL-36b or IL-36c cytokine stimulation following 8 or

24 h of treatment (10 ng mL�1, false discovery rate < 0.10,

fold change > 2.00 or < 0.05). There was strong correlation

between IL-36a, IL-36b and IL-36c and between IL-36 and

IL-1b responses at both 8 and 24 h. We identified a core set

of 225 differentially expressed genes common to the IL-1band IL-36 cytokines with similar early (8 h) and late (24 h)

responses. These were associated with leucocyte chemotaxis,

mucosal immunity and neutrophil activation. Genes induced

by IL-1b and IL-36 had prominent overlap with genes altered

in both plaque and pustular psoriasis (P = 3.9 9 10�14 and

P = 5.7 9 10�26, respectively). Furthermore, IL-1b/IL-36-increased differentially expressed genes overlapped

significantly (P < 10�5) with genes near known psoriasis

genome-wide association loci (e.g. TNFAIP3, ETS1, TNIP1 and

ZC3H12C). IL-1b and IL-36 induced expression of mRNAs

encoding the ligands IL1A, IL1B, IL36A, IL36B and IL36G,

demonstrating that these cytokines have the ability to regulate

their own expression positively. We also noted increased

expression of cathepsin S, which cleaves and activates IL-36

cytokines, along with elevated expression of proteins encoding

receptor subunits (IL1RAP) and downstream signalling ele-

ments (IRAK2, MYD88, TAB2). Transcription responses also

included negative feedback regulators, with increased expres-

sion of genes encoding receptor antagonists (IL1RN, IL36RN),

anti-inflammatory ligands (IL37, IL38) and a decoy receptor

(IL1R2). Both IL-1 and IL-36 responses were dependent upon

MYD88 signalling, as complete knockout of MYD88 by

CRISPR/Cas9 mutagenesis completely abrogated IL-36 sig-

nalling. Transcription factor analyses using a dictionary of

2934 motifs identified over-representation of motifs associated

with transcription factors from the ETS, SOX, GATA, JUN,

FOS and nuclear factor (NF)-jB families of transcription fac-

tors. These findings were validated by small interfering RNA

knockdown of ETS1 and NF-jB. These data provide the most

comprehensive assessment available of the effects of the IL-1

and IL-36 cytokines in keratinocytes. Our findings suggest that

the transcriptional responses of IL-1 and IL-36 rebalance IL-1/

IL-36 signalling through both positive and negative feedback.

Targeting IL-36 cytokine responses in keratinocytes may lead

to novel approaches to treat psoriasis and its clinical subtypes.

FC26Effectiveness, drug survival and safety of fumaricacid esters for moderate-to-severe psoriasis inroutine care: results from the German PsoriasisRegistry PsoBestM. Augustin,1 U. Mrowietz,2 M.A. Radtke,3 D. Thaci,4

K. Ralph,5 A. K€orber6 and K. Reich71Institute and German Center of Health Services Research in Dermatology,

University Medical Center of Hamburg, Hamburg, Germany; 2Department of

Dermatology, University of Kiel, Kiel, Germany; 3IVDP, University of

Hamburg, Hamburg, Germany; 4Department of Dermatology, University of

Schleswig-Holstein, L€ubeck, Germany; 5Dermatology Practice, Selters,

Germany; 6Department of Dermatology University of Essen, Essen, Germany

and 7Dermatologikum, Hamburg, GermanyFumaric acid esters (FAEs) are the most frequently prescribed

antipsoriatic systemic drugs in Germany. Currently, new com-

pounds of fumaric acid are licensed in Europe and North

America. Furthermore, FAEs are licensed globally for multiple

sclerosis. The study objective was the evaluation of effective-

ness, drug survival and safety of FAEs for psoriasis under rou-

tine care conditions in the German national registry PsoBest

compared with other nonbiological systemic drugs. The Ger-

man National Psoriasis Registry PsoBest evaluates the long-

term outcomes of patients receiving systemic antipsoriatic

treatments. To date, 824 dermatology private practices and

clinics are subscribed. It was founded in 2008 and more than

7000 patients have been recruited. For this analysis, patients

naive to the respective drugs (FAE vs. other systemics) were

observed for 12 months after first exposure. Adverse events

and serious adverse events were calculated as observed. In total

1318 patients reflecting 1807 patient-years (PY) on FAEs and

1302 control patients (2674 PY; 76.6% methotrexate, 17.4%

ciclosporin, 5.2% retinoids, 0.8% others) were included. The

mean age was 45.7 years (FAEs) and 48.9 years (controls);

40.6% (FAEs) and 41.7% (controls) were female. Patient

numbers at 3, 6 and 12 months were 785, 590 and 395 for

FAEs and 824, 610 and 365 for controls. For the FAE vs. con-

trol groups the mean treatment duration was 9.4 vs.

11.0 months, mean body mass index 28.0 vs. 28.5 kg m�2,

mean baseline Psoriasis Area and Severity Index (PASI) 13.9

vs. 14.2, mean Dermatology Life Quality Index (DLQI) 11.0

in both cohorts, and rate of psoriatic arthritis 5.2% vs. 24.7%.

Outcomes for the time points 3, 6 and 12 months were PASI

75, 25.0%, 47.8% and 54.2% for FAEs and 35.9%, 45.7% and

51.0% for controls; and DLQI 5.5, 3.8 and 3.0 for FAEs and

5.5, 4.3 and 3.7 for controls. There were no statistically sig-

nificant differences in serious adverse events; and no differ-

ences in adverse events except higher rates of gastrointestinal

infections (13.1 vs. 8.4 per 100 PY) and blood and lymphatic

disorders for FAEs (4.1 vs. 1.0 per 100 PY), and lower





from gene to clinic

71ABSTRACTS

infection rates for FAEs (3.0 vs. 6.0 per 100 PY and 8.4 vs.

13.1 per 100 PY). The median drug survival for FAEs was

54.8, compared with 51.1 months for other nonbiological

treatments (P = 0.40). Side-effects were the most frequent

reason for early discontinuation of FAEs. In conclusion, FAEs

in psoriasis routine treatment show markedly different base-

line profiles and distinct differences in adverse events, but

similar rates of serious adverse events, outcomes and drug sur-

vival in the first 12 months compared with other systemics.

FC27The lymphatic system plays an important role inthe migration of pathogenic T cells towardssynovial joints and entheses in psoriasisD. Verhaegh,1,2 E. Prens,3 A.M.C. Mus,2

P.S. Asmawidjaja,2 N. Davelaar,2 A. Hofman,4 J.-B. Jaquet,4 J.M.W. Hazes,2 M.R. Kok,1 E. Lubberts2

and R.J. Bisoendial1,21Department of Clinical Immunology and Rheumatology and 4Department of

Plastic Surgery, Maasstad Hospital, Rotterdam, the Netherlands and2Department of Rheumatology and 3Department of Dermatology, Erasmus

University Medical Center, Rotterdam, the NetherlandsPsoriasis is characterized by acanthosis, impaired immune cell

migration and remodelling of the vascular and lymphatic sys-

tem. Up to 30% of patients with psoriasis develop psoriatic

arthritis (PsA). The lymphatic system may control the migra-

tion of pathogenic T cells to either skin or synovial joints and

entheses. In this study human dermal lymphatic endothelial

cells (LECs; 0.5 9 104) and fibroblast-like synoviocytes of a

patient with PsA (PsA-FLS; 1.0 9 104) were preincubated for

3 days with media or PsA synovial fluid (PsA-SF; 20% v/v).

Then, LECs or PsA-FLS were cocultured with 2.5 9 104

CD4+ CD45RO+ CD25�/lo T cells that were sorted from

healthy donors with or without stimulation with aCD3/aCD28. After 72 h, T cells were immunophenotyped by flow

cytometry. Relevant T helper (Th) subsets were characterized,

including the CCR6+ subsets Th17.1 (CCR4� CXCR3+),

Th17/Th22 (CCR4+ CXCR3�), Th17 (CCR4+ CXCR3�

CCR10�) and Th22 (CCR4+ CXCR3� CCR10+). We also

looked at cutaneous lymphocyte-associated antigen (CLA), a

skin-homing receptor. Interleukin (IL)-17A, tumour necrosis

factor (TNF) and IL-22 protein levels in the cocultures were

determined by enzyme-linked immunosorbent assay. Stimula-

tion of CD4+ CD45RO+ T cells in coculture with PsA-FLS

skewed towards the CCR6+ subset Th17/Th22, which were

predominantly Th17 cells. Th17 differentiation was suppressed

in coculture with LECs even when LECs were activated upon

preincubation with PsA-SF. Stimulation of CD4+ CD45RO+ T

cells in coculture with LEC, as compared with PsA-FLS, pro-

moted the generation of the Th22 subset. Upon coculture,

activated LECs conserved CLA expression on stimulated

CD4+ CD45RO+ T cells at a higher level than PsA-FLS, partic-

ularly in the CCR6+ T-cell subset. In line with the fluores-

cence-activated cell sorting results, lower IL-17A levels and a

trend towards higher IL-22 levels were observed in the cocul-

tures with LEC, compared with the coculture with PsA-FLS.

No differences were seen for TNF protein levels. Further

investigation of the underlying mechanisms revealed an

important role for the lymphotoxin b receptor (LTbR) path-

way and the Notch ligand delta-like 4 during the coculture

experiments of the CD4+ CD45RO+ T cells with LECs. In con-

clusion, LECs are directly involved in T-cell differentiation and

homing capabilities, as shown by suppression of Th17 differ-

entiation in coculture experiments, compared with PsA-FLS.

Also, LECs promoted Th22 generation and conserved CLA

expression in CCR6+ T cells. The LTbR pathway and delta-like

4 may be involved in LEC-mediated modulation of T-cell

homing and deserve further exploration.

FC28Systemic inflammation and evidence of acardiosplenic axis in patients with psoriasisK.F. Hjuler,1 L.C. Gormsen,2 M.H. Vendelbo,2

A. Egeberg,3 J. Nielsen1 and L. Iversen1

1Department of Dermatology and 2Department of Nuclear Medicine and PET

Centre, Aarhus University Hospital, Aarhus, Denmark and 3Department of

Dermatology and Allergy, Herlev and Gentofte Hospital, University of

Copenhagen, Copenhagen, DenmarkPsoriasis has been associated with cardiovascular comorbidi-

ties, and a direct contribution from psoriatic inflammation

unrelated to traditional cardiovascular risk factors has been

suggested. Studies of soluble biomarkers of systemic inflam-

mation have shown evidence of mild systemic inflammation

in patients with psoriasis compared with healthy controls.

However, it is still not fully elucidated to what extent psoriasis

causes systemic inflammation, whether this is clinically rele-

vant, and whether this causally leads to premature cardiovas-

cular disease. Based on preclinical and cardiovascular clinical

data a central role of the spleen in the progression of

atherosclerotic disease has been suggested and conceptualized

as the ‘cardiosplenic axis’. Furthermore, it has been shown

that splenic inflammation assessed by 18F-fluorodeoxyglucose

(FDG) positron emission tomography (PET) computed

tomography (CT) is increased in patients with autoimmune

and inflammatory diseases, and that the splenic FDG uptake

correlates with measures of systemic inflammation. In this

observational, controlled clinical study we aimed to assess

splenic FDG uptake as a measure of systemic inflammation in

untreated patients with moderate-to-severe psoriasis compared

with retrospectively matched controls assessed by FDG-PET/

CT. A secondary objective was to investigate associations

between splenic activity and aortic and subcutaneous adipose

tissue inflammation. We included patients with moderate-to-

severe psoriasis (n = 12, mean age 61.4 � 4.1 years, 83%

men, mean Psoriasis Area Severity Index 14.5 � 4.3) and

matched controls (n = 23, age 60.4 � 4.5 years, 87% men).

Splenic inflammation was measured using the background-

corrected spleen liver ratio (SLR) based on mean standardized

uptake values. Aortic inflammation was previously assessed in

the patient cohort as the target-to-background ratio (TBR) of

the whole vessel. The mean SLR was increased in patients with

psoriasis compared with controls (mean SLR 0.94 � 0.11 vs.



0.82 � 0.08, P= 0.001. A significant association between SLR

and aortic mean whole vessel TBR was found in patients with

psoriasis (Pearson r = 0.65, P= 0.02). A significant association

between SLR and subcutaneous adipose tissue inflammation

was also found in the population overall. Our data confirm

the existence of systemic inflammation in patients with psoria-

sis beyond that ascertained in previous biomarker studies, and

provide the rationale for a mechanistic link between psoriasis-

driven inflammation and cardiovascular comorbidity through a

spleen–atherosclerotic axis. The cardiosplenic axis may mecha-

nistically, at least in part, explain the epidemiological observa-

tion that patients with psoriasis have an increased risk of heart

disease.

FC29Efficacy and safety of risankizumab, an interleukin-23 inhibitor, in patients with moderate-to-severechronic plaque psoriasis: 16-week results from thephase III IMMhance trialA. Blauvelt,1 K.A. Papp,2 M. Gooderham,3,4

R.G. Langley,5 C. Leonardi,6 J.-P. Lacour,7 S. Philipp,8

S. Tyring,9 M. Bukhalo,10 J.J. Wu,11 J. Bagel,12

E.H. Frankel,13 D. Pariser,14 M. Flack,15 J. Scherer,15

Z. Geng,16 Y. Gu,16 A. Camez17 andE.H.Z. Thompson181Oregon Medical Research Center, Portland, OR, U.S.A.; 2K Papp Clinical

Research and Probity Medical Research, Waterloo, ON, Canada; 3School of

Medicine, Queen’s University, Kingston, ON, Canada; 4Centre for

Dermatology and Probity Medical Research, Peterborough, ON, Canada;5Dalhousie University, Halifax, NS, Canada; 6St Louis University, St Louis,

MO, U.S.A.; 7Hopital de l’Archet, University of Nice–Sophia Antipolis,Nice, France; 8Charit�e Universit€atsmedizin Berlin, Berlin, Germany;9University of Texas Health Science Center and Center for Clinical Studies,

Houston, TX, U.S.A.; 10Altman Dermatology Associates, Arlington Heights,

IL, U.S.A.; 11Kaiser Permanente Los Angeles Medical Center, Los Angeles,

CA, U.S.A.; 12Psoriasis Treatment Center of Central New Jersey, East

Windsor, NJ, U.S.A.; 13RISkinDoc, Cranston, RI, U.S.A.; 14Eastern Virginia

Medical School and Virginia Clinical Research Inc., Norfolk, VA, U.S.A.;15Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, U.S.A.,16AbbVie Inc., North Chicago, IL, U.S.A.; 17AbbVie Deutschland GmbH &

Co KG, Ludwigshafen, Germany and 18AbbVie Inc., Redwood City, CA,

U.S.A.Interleukin (IL)-23, a key regulator of multiple effector cyto-

kines [including IL-17, IL-22 and tumour necrosis factor

(TNF)], is thought to drive the development and maintenance

of psoriatic lesions. Risankizumab is a potent humanized IgG1

monoclonal antibody that inhibits IL-23 by specifically bind-

ing its p19 subunit. In a phase II trial, the efficacy and safety

of risankizumab were compared with those of ustekinumab,

an IL-12/IL-23 inhibitor, in patients with moderate-to-severe

chronic plaque psoriasis (Papp KA, Blauvelt A, Bukhalo M et al.

Risankizumab versus ustekinumab for moderate-to-severe pla-

que psoriasis. N Engl J Med 2017; 376: 1551–60). The primary

end point of ≥ 90% improvement in Psoriasis Rea and Severity

Index (PASI 90) at week 12 was achieved by a significantly

higher proportion of patients receiving risankizumab (77%,

pooled 90 + 180 mg doses) compared with ustekinumab

(40%). In addition, adverse events were similar between the

risankizumab and ustekinumab groups through week 48, sug-

gesting a comparable safety profile. Currently, multiple phase

III studies are in progress to investigate the efficacy and safety

of risankizumab in patients with moderate-to-severe chronic

plaque psoriasis. IMMhance (NCT02672852) is a phase III

multicentre, randomized, double-blind, placebo-controlled

trial evaluating the efficacy and safety of risankizumab vs. pla-

cebo in patients with moderate-to-severe chronic plaque psori-

asis. The initial 16-week placebo-controlled period was

followed by randomized withdrawal and subsequent re-treat-

ment with risankizumab. Randomization was stratified by

weight and prior TNF inhibitor exposure. The coprimary end

points were percentages of patients achieving PASI 90 and sta-

tic Physician’s Global Assessment 0 or 1 at week 16; missing

data were imputed as nonresponders. At baseline, 507 patients

at 60 sites were randomized 4 : 1 to receive either risankizu-

mab (150 mg at weeks 0 and 4) or placebo during the 16-

week placebo-controlled period. Baseline demographics and

disease characteristics from a preliminary analysis of the study

database are presented here. The mean age was 49.2 years and

mean weight was 92.0 kg; 70.2% of patients were male. A

history of diagnosed or suspected psoriatic arthritis was

reported in 34.5% of patients, and prior TNF inhibitor therapy

was reported in 36.5% of patients. The mean baseline PASI

and body surface area were 20.1 and 26.1%, respectively. Effi-

cacy and safety data from the IMMhance trial through

16 weeks (not yet available at the time of abstract submission)

will be presented. The results from a phase III trial of risanki-

zumab in patients with moderate-to-severe chronic plaque

psoriasis will be publicly revealed for the first time.

FC30Quality of care and use of systemic drugs forpsoriasis in the past 12 years: results from a seriesof nationwide health care studies in GermanyM. Radtke,1 M. Augustin1 and K. Reich21Institute and German Center for Health Services Research in Dermatology,

University Medical Center, Hamburg, Germany and 2Dermatologikum,

Hamburg, GermanySince the intervention of the first biological drugs for psoriasis

in 2005, the landscape of psoriasis health care has markedly

changed in most countries. In particular, there has been a dra-

matic increase in the potential of reaching normal quality of

life and good health status in patients with moderate-to-severe

disease. Nevertheless, in most countries there persist discrep-

ancies between the guideline recommendations for psoriasis

treatment and real-world health care: many patients with high

needs do not yet get appropriate healthcare. In Germany, the

quality of health care for psoriasis was very critical in 2005.

Most patients lacked sufficient care and only a minor portion

received systemic drugs. In the meantime, a national psoriasis

programme has been conducted in order to improve the qual-

ity of psoriasis care, including development of an evidence-

based guideline, a consensus of treatment goals, the invention





from gene to clinic

73ABSTRACTS

of a ‘culture of measurement’ and consensus national goals

for psoriasis care. These measures were supported by the

establishment of 30 regional psoriasis networks involving

more than 800 dermatologists. The outcomes of this national

psoriasis programme are evaluated on a regular basis. The cur-

rent analysis shows the long-term results of the programme,

including the results of the very recent survey from 2017. All

surveys were based on random samples of dermatology prac-

tices and clinics across the country. In each survey in 2004,

2008, 2014 and 2017, between 120 and 150 centres were

nominated, and data from patients and dermatologists were

obtained from a minimum of 1500 patients per survey,

including psoriasis characteristics, Psoriasis Area and Severity

Index (PASI), Dermatology Life Quality Index (DLQI), patient

benefit index, patient satisfaction and current and previous

treatments. Between 2004 and 2017 there was a significant

increase in the proportion of patients reaching sufficient qual-

ity of health care from 34% to 79% (total n = 6323). The

mean PASI reduced from 11.4 to 7.4, DLQI reduced from 8.6

to 5.6, and the proportion of patients with severe disease

dropped from 17.8% to 8.6%. With respect to drug treatment,

there has been a significant annual increase in the drug vol-

umes for systemic treatments by about 24% per year, with

€348 million in 2010 to €761 million in 2015. Despite these

significant increases in the use of systemic drugs for psoriasis,

there remain large regional disparities, with some federal

states spending more than €6.00 per capita of population for

biologics in psoriasis compared with €0.90 in others. Besides

regional disparities, there are also severe differences in access

to modern drugs between patients referring to a dermatologist

(> 70% chance of guideline-compliant treatment) compared

with GPs (< 40%). In conclusion, there has been a marked

increase in the proportion of patients with psoriasis receiving

guideline-compliant care, in particular systemic treatments for

moderate-to-severe disease. Nevertheless, many patients are

still lacking access to treatments. The national conference on

psoriasis care has thus decided to reconfirm the national

healthcare goals for psoriasis in the next 5 years with higher

thresholds to reach.

FC31Efficacy and safety of mirikizumab (LY3074828) inthe treatment of moderate-to-severe plaquepsoriasis: results from a phase II studyK. Reich,1,2 R. Bissonnette,3 A. Menter,4

P. Klekotka,5 D. Patel,5 J. Li,5 J. Tuttle5 andK. Papp6,71Dermatologikum Hamburg, G€ottingen, Germany; 2Georg-August-University,

G€ottingen, Germany; 3Innovaderm Research, Montreal, QC, Canada;4Department of Dermatology, Baylor University Medical Center, Dallas, TX,

U.S.A.; 5Eli Lilly and Company, Indianapolis, IN, U.S.A.; 6Papp Clinical

Research, Waterloo, ON, Canada and 7Probity Medical Research, Waterloo,

ON, CanadaInterleukin (IL)-23 is a cytokine involved in the pathogenesis

of psoriasis. In this phase II (AMAF, NCT02899988), multi-

centre, randomized, double-blind, placebo-controlled trial, we

investigated the efficacy and safety of different dose groups of

mirikizumab (LY3074828), a p19-directed interleukin-23

antibody, in patients with moderate-to-severe plaque psoriasis.

Mirikizumab is the United States Adopted Name, pending final

approval by the World Health Organization. Adult patients

with moderate-to-severe psoriasis were randomized at a

1 : 1 : 1 : 1 ratio to receive placebo (n = 52) or mirikizumab

30 mg (n = 51), 100 mg (n = 51) or 300 mg (n = 51) at

weeks 0 and 8. The primary objective was to evaluate the

superiority of mirikizumab over placebo in achieving ≥ 90%

improvement in Psoriasis Area and Severity Index (PASI 90)

response at week 16. Additional secondary objectives included

evaluation of superiority of mirikizumab to placebo in achiev-

ing PASI 75 and PASI 100 at week 16. Comparisons were

done using logistic regression analysis with treatment, geo-

graphical region and previous biological therapy in the model.

Missing data were imputed as nonresponse. Only selected data

are presented to avoid a potential impact on the ongoing

blinded study. Baseline characteristics were generally well bal-

anced across treatment arms. The primary efficacy end point

at week 16 was met for each dose group with PASI 90

responses of 0%, 29.4% (P < 0.01), 58.8% (P < 0.001) and

66.7% (P < 0.001), respectively, for patients treated with pla-

cebo and mirikizumab 30 mg, 100 mg and 300 mg. PASI

75/100 responses at week 16 were 52.9% (P < 0.001)/

15.7% (P < 0.05), 78.4% (P < 0.001)/31.4% (P < 0.01) and

74.5 (P < 0.001)/31.4% (P < 0.01) for the mirikizumab

30 mg, 100 mg and 300 mg groups, respectively, compared

with 3.8%/0% for the placebo group. During the 16-week

induction period, two (1.0%) patients discontinued the study

due to adverse events. There were two (1.3%) serious adverse

events in mirikizumab-treated patients compared with one

(1.9%) in placebo-treated patients. In conclusion, the week 16

PASI responses were highest in the 100-mg and 300-mg

mirikizumab treatment arms. Responses in all mirikizumab

treatment arms were significantly higher than with placebo.

The overall frequency of adverse events was similar for mirik-

izumab- and placebo-treated patients.

FC32Certolizumab pegol for the treatment of patientswith moderate-to-severe chronic plaque psoriasis:an overview of three randomized controlled trialsA. Blauvelt,1 K. Reich,2 M. Lebwohl,3 D. Burge,4

C. Arendt,5 L. Peterson,6 J. Drew,4 R. Rolleri6 andA. Gottlieb71Oregon Medical Research Center, Portland, OR, U.S.A.; 2Dermatologikum

Hamburg and SCIderm Research Institute, Hamburg, Germany; 3Icahn School

of Medicine at Mount Sinai, New York, NY, U.S.A.; 4Dermira, Inc., Menlo

Park, CA, U.S.A., 5UCB Pharma, Brussels, Belgium; 6UCB BioSciences,

Inc., Raleigh, NC, U.S.A. and 7New York Medical College, Valhalla, NY,

U.S.A.Certolizumab pegol (CZP), the only PEGylated, Fc-free, anti-

TNF biologic, is currently under development for treatment of

psoriasis and has demonstrated promising results in phase II

trials. Three 144-week, phase III, multinational, randomized,



double-blinded trials of CZP in adults with moderate-to-severe

chronic plaque psoriasis are currently ongoing: CIMPASI-1

(NCT02326298) and CIMPASI-2 (NCT02326272) are replicate

placebo-controlled trials, and CIMPACT (NCT02346240) is an

active- and placebo-controlled trial. Pooled results for CZP vs.

placebo from the first 16 weeks of CIMPASI-1, CIMPASI-2 and

CIMPACT are reported here. Patients in all studies were aged

≥ 18 years and had moderate-to-severe chronic plaque psoria-

sis for ≥ 6 months, Psoriasis Area and Severity Index (PASI) ≥12, body surface area affected ≥ 10% and Physician’s Global

Assessment (PGA ≥ 3), and were candidates for systemic ther-

apy. Pooled end points (week 16) included PASI 75 (≥ 75%

reduction from baseline), PGA 0/1 (‘clear’ or ‘almost ‘clear’

with ≥ 2-category improvement) and PASI 90 response. Safety

for all three studies was examined via treatment-emergent

adverse event (TEAE) monitoring. In the combined studies,

342 patients were randomized to CZP 400 twice weekly

(Q2W), 351 to CZP 200 Q2W and 157 to placebo. Demo-

graphic and baseline disease characteristics were similar across

treatment groups, and most patients were in their mid-40s

(mean 45.7 years, median 46.0), white (94%) and male

(63.9%). At week 16, more CZP 400 mg- and CZP 200 mg-

treated patients vs. placebo-treated patients were PASI 75

responders (CZP 400 mg Q2W: 80.1%, CZP 200 mg Q2W:

74.5%, placebo: 7.5%; P < 0.001 for both), PGA 0/1 respon-

ders (CZP 400 mg Q2W: 63.7%, CZP 200 mg Q2W: 54.6%,

placebo: 2.8%; P < 0.001 for both) and PASI 90 responders

(CZP 400 mg Q2W: 52.2%; CZP 200 mg Q2W: 44.5%; pla-

cebo: 1.6%; P < 0.001 for both). TEAEs for both doses of CZP

were infrequent and consistent with the known safety profile

of CZP and anti-TNF therapy, and serious TEAEs and serious

infections and infestations were rare across treatment groups

(CZP 400 mg Q2W: 4.7% and 0.6%, respectively; CZP

200 mg Q2W: 1.4% and 0%; placebo: 4.5% and 0%). No

deaths were reported in any of the three studies through week

16. In the phase III programme, treatment with CZP 400 mg

Q2W and 200 mg Q2W were associated with statistically sig-

nificant, clinically meaningful improvements in moderate-to-

severe chronic psoriasis, including a PASI 75 responder rate of

> 80% in the CZP 400 mg Q2W group. This study was

funded by Dermira, Inc. Dermira and UCB are in a strategic

collaboration to evaluate the efficacy and safety of cer-

tolizumab pegol in the treatment of moderate-to-severe plaque

psoriasis. Medical writing support was provided by Prescott

Medical Communications Group (Chicago, IL). All costs

associated with development of this abstract were funded by

Dermira, Inc.

FC33Switching or restarting of tumour necrosis factor-ainhibitors after interruption under daily-lifeconditions: efficacy report from the AustrianPsoriasis Registry (PsoRA)P. Wolf,1 W. Weger,1 L. Richter,2 A. Mlynek,3

P. Sator,4 W. Saxinger,5 G. Ratzinger,6 C. K€olli,7

C. Painsi,8 C. Bangert,9 R. Tatarski,10

M. Sch€utz-Bergmayr,11 P. Ponholzer,12

F. Trautinger,13 R. Strohal,14 R. M€ullegger,7

M. Inzinger,1 R. Lichem,1 W. Salmhofer1 andF. Quehenberger11Medical University of Graz, Graz, Austria; 2State Hospital of Vienna

Rudolfstiftung, Vienna, Austria; 3Hospital of Elisabethinen, Linz, Austria;4Hospital of Hietzing, Vienna, Austria; 5Hospital of Wels-Grieskirchen,

Wels, Austria; 6Medical University of Innsbruck, Innsbruck, Austria; 7State

Hospital, Wiener Neustadt, Wiener Neustadt, Austria; 8State Hospital,

Klagenfurt, Klagenfurt, Austria; 9Medical University of Vienna, Vienna,

Austria; 10Paracelsus Private Medical University Salzburg, Salzburg, Austria;11Johannes Kepler University Linz, Linz, Austria; 12Donauspital, SMZ OST,

Vienna, Austria; 13Karl Landsteiner University of Health Sciences, St. P€olten,

Austria and 14Federal Academic Teaching Hospital, Feldkirch, Feldkirch,

AustriaWe were interested in investigating how well tumour necrosis

factor (TNF)-a inhibitors act after switching or restarting after

interruption under daily-life conditions. A data export by

2016 from the Austrian Psoriasis Registry (PsoRA) revealed

that 141 patients fulfilled the inclusion criteria for this analy-

sis: (i) TNF-a inhibitor treatment duration of 3 months or

longer, (ii) switch to another TNF-a inhibitor, (iii) treatment

interruption of 3 months or longer before restarting with the

same TNF-a inhibitor and (iv) availability of complete data to

perform the analysis. Response to treatment in the registry is

recorded in treatment categories: 1, CR (complete remission);

2, ≥ 90% improvement in Psoriasis Area and Severity Index

(PASI) 90; 3, PASI 75; 4, PASI 50 or 5, PASI < 50. Reasons

for treatment interruption, with a mean time of 6.4, 10.1 and

10.2 months for infliximab (IFX), adalimumab (ADA) and

etanercept (ETA), respectively, were due mainly to complete

remission, patient wish or other; reasons for switching were

primarily for ineffectiveness or loss of initial response. The

main switch/restart combinations were ETA>ADA n = 72,

ADA>ETA n = 20, ADA>ADA n = 12 and ETA>ETA n = 12.

The treatment response (measured in PASI reduction category)

improved by 0.97 (from 4.49 to 3.51; P < 0.001) in

ETA>ADA switchers and by 1.05 (from 4.10 to 3.05;

P = 0.035) in ADA>ETA switchers. Intriguingly, there was a

trend for loss of efficacy in the ADA>ADA restarters by �1.08

(from 1.58 to 2.67; P = 0.055), whereas in the ETA>ETArestarters efficacy was sustained (2.75 vs. 2.75, P = 1.0), com-

paring the outcome after the first treatment cycle vs. the sec-

ond cycle. For IFX, the case numbers of the groups of were

too low (n < 10) to be included in the statistical analysis.

These data generated under daily-life conditions are consistent

with the notion that after an initial unsatisfactory treatment

response, switching either from ETA to ADA or from ADA to

ETA can result in an improved treatment outcome. Moreover,

the data also support the concern that after treatment interrup-

tion, restarting with ADA (e.g. due to neutralizing antibodies)

but not with ETA may result in a weaker treatment response.





from gene to clinic

75ABSTRACTS

Posters

P001Evaluation of serum uric acid among patients withpsoriasis in a developing countryS.D. Joshi1 and L. Limbu21Far Western Community Hospital, Attariya, Nepal and 2Sahid Memorial

Hospital, Kathmandu, NepalPsoriasis is a common chronic inflammatory skin disorder.

Studies have shown that psoriasis can progress to systemic

involvement such as in psoriatic arthritis, metabolic syn-

drome, and uric acid and lipid metabolism derangement. The

aim of this study was to evaluate serum uric acid levels

among patients with psoriasis. From the departments of der-

matology of two tertiary-care hospital in Kathmandu, 138

patients were enrolled in the study. Among them were 69

patients with psoriasis selected as cases, 36 male and 33

female; 69 patients with other dermatological diseases after

matching age and sex were selected as controls. After

informed written consent was received, a full detailed history

and physical examination was conducted, and determination

of the body mass index (BMI) and Psoriasis Area and Severity

Index (PASI) of cases was calculated. Serum samples of both

cases and controls were sent for uric acid investigation.

Chronic plaque psoriasis was the most common variant (60,

87%), and there was no significant association between psori-

asis type and sex. The male-to-female ratio was 1.1 : 1. The

majority of the patients with psoriasis (76%) were among the

younger population, and most of them (91%) had a normal

serum uric acid level. Most of the patients (55, 80%) did not

have a family history of psoriasis. Most patients (58, 84%)

had history of a flare-up in the winter season. BMI was found

to be in the normal range in most of the patients (65, 94%).

Among the control group, eczema was the most common

diagnosis (16, 23%), and most of the patients (91%) had

normal serum uric acid levels. No significant association

between PASI score and serum uric acid level was found in

the study (P = 0.81). Most of the patients had aggravation of

psoriasis in winter. However, serum uric acid was not signifi-

cantly associated with PASI, which may be due to psoriasis

lesions not being severe or, extensive body surface area

involvement and no systemic complication issues. However,

we have to rule out other systemic complications due to pso-

riasis in a long-term follow-up.

P002A transcriptomic study investigating thepathogenesis of generalized pustular psoriasisM. Catapano,1,2 F. Capon,1 F. Ciccarelli12 andJ. Barker11King’s College London, London, U.K. and 2The Francis Crick Institute,

London, U.K.

Generalized pustular psoriasis (GPP) is a rare form of psoriasis

manifesting with episodic flares of widespread skin pustulation

and systemic inflammation. Although the pathogenesis of GPP

remains poorly understood, genetic studies have identified

mutations in AP1S3, CARD14 and IL36RN, indicating an involve-

ment of innate, autoinflammatory pathways that appear to be

distinct from those causing psoriasis vulgaris. The aim of our

study was to investigate the molecular pathogenesis of GPP, as

well as its overlap with psoriasis and autoinflammatory dis-

eases. To achieve this purpose, we generated whole-blood

RNA sequencing data on nine cases of GPP cases and seven

sex- and age-matched controls. We also accessed publicly

available transcriptome datasets, relating to psoriasis or autoin-

flammatory syndromes mediated by interleukin-1 (cryopyrin-

associated periodic syndrome, CAPS) or type I interferon

(chronic atypical neutrophilic dermatosis with lipodystrophy

and elevated temperature, CANDLE). We analysed all expres-

sion profiles using DESeq2, limma and Ingenuity Pathway

Analysis. The analysis of the GPP whole-blood transcriptome

identified 86 genes that were upregulated in patients com-

pared with controls (fold-change 1.5, false discovery rate

< 0.05). These differentially expressed genes showed no sig-

nificant overlap with those that are overexpressed in psoriasis

(P = 0.057) or CAPS (P = 0.07). Conversely, the proportion

of upregulated genes shared between GPP and CANDLE was

highly significant (P = 3.2 9 10�7). Moreover, pathway

enrichment analysis of the 86 genes upregulated in GPP high-

lighted a strong type I interferon signature (false discovery

rate = 8.7 9 10�6). In keeping with this observation, the

combined expression of five key IFN-induced genes (IFI6,

IFIT3, IFITM3, OASL and PLSCR1) was higher in cases than in

controls (P < 0.05). In conclusion, our results confirm the

notion of abnormal innate immune regulation in GPP and

warrant further investigations of type I interferon signalling in

this disease.

P003Patient perception and the importance of clear/almost clear skin as a treatment goal in moderate-to-severe plaque psoriasis: results of the ‘Clearabout Psoriasis’ worldwide patient surveyA. Armstrong,1 S. Jarvis,2 W.-H. Boehncke,3

M. Rajagopalan,4 P. Fern�andez-Pe~nas,5 R. Romiti,6

A. Bewley,7 M. O’Donnell,8 L. Huneault,8 E. Dekker,8

M. Sodha9 and R.B. Warren10

1Department of Dermatology, University of Southern California, Los Angeles,

CA, U.S.A.; 2Richford Gate Medical Practice, London, U.K.; 3Division of

Dermatology and Venereology, Geneva University Hospital, and Department of

Pathology and Immunology, Faculty of Medicine, University of Geneva,

Geneva, Switzerland; 4Department of Dermatology, Apollo Hospitals, Chennai,



India; 5Department of Dermatology, Westmead Hospital, The University of

Sydney, Westmead, Australia; 6Department of Dermatology, Hospital das

Cl�ınicas University of S~ao Paulo, S~ao Paulo, Brazil; 7Whipps Cross

University Hospital and the Royal London Hospital, London, U.K.; 8Novartis

Pharma AG, Basel, Switzerland; 9GfK, Basel, Switzerland and 10The

Dermatology Centre, Salford Royal NHS Foundation Trust, The University of

Manchester, Manchester Academic Health Science Centre, Manchester, U.K.With the advent of new and increasingly effective therapies,

clear/almost clear skin is now recognized by dermatologists as

the optimal treatment standard in patients with psoriasis.

However, limited data exist on patient perception of the effi-

cacy of psoriasis therapies and whether clear/almost clear skin

is attainable. The ‘Clear about Psoriasis’ worldwide survey was

conducted in patients with moderate-to-severe plaque psoriasis

to assess patient perception of the disease in terms of treat-

ment satisfaction, clinical outcomes and the importance of

clear/almost clear skin. The survey was conducted from Octo-

ber 2015 to March 2016 in adult patients with moderate-to-

severe plaque psoriasis [self-reported Psoriasis Area and Sever-

ity Index (PASI) ≥ 10 or PASI 5–10 with impact of psoriasis

on sensitive/prominent body parts: face, palms, hands, fin-

gers, genitals, soles of feet or nails] from 31 countries in Asia,

Australia, Europe, North America and South America. Of 8338

patients included in the survey, the mean age was 44 years

and 55% were female. The majority of the patients were

employed (67%), married (55%) and had self-reported psori-

atic arthritis (51%). The mean self-reported PASI score was

14.3; 68% had PASI score ≥ 10 and 32% had PASI score 5–10. Overall, 56% of patients were satisfied with their current

treatment, 20% were dissatisfied and 24% were uncertain.

Most patients (57%, n = 4733) did not achieve clear/almost

clear skin with their current therapy; among them, 56% dis-

agreed that clear/almost clear skin was a realistic aspiration.

Among respondents who had achieved clear/almost clear skin

(43%, n = 3605) with their current treatment, 53% did not

believe that clear/almost clear skin was possible before actu-

ally achieving this goal. Furthermore, 73% of respondents

with self-reported clear/almost clear skin initiated their cur-

rent efficacious treatment > 1 year after diagnosis; of these

28% had to wait > 5 years. The majority of patients (84%)

experienced discrimination and/or humiliation due to psoria-

sis, 43% patients believed that psoriasis had affected their past

or current relationships, and 54% felt that psoriasis had

impacted their professional life. Among employed patients

(n = 5537), 42% needed ≥ 1 day off from work in the previ-

ous 6 months due to psoriasis, and 16% needed ≥ 10 days

off. Patients who had not achieved clear/almost clear skin

reported that such an achievement would open new possibili-

ties, like lying on a beach/sunbathing (59%), swimming

(58%) and a wider choice of clothing (40%). The ‘Clear

about Psoriasis’ survey highlights the importance of clear/al-

most clear skin to patients with psoriasis and the persistence

of inadequate treatment, even with the availability of effective

therapeutics. This study was sponsored by Novartis Pharma-

ceuticals.

P004Immunogenicity with tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, in a pooledanalysis of three randomized controlled trials inpatients with chronic plaque psoriasisA. Kimball,1 A. Blauvelt,2 K. Reich,3 Q. Li,4 F. vanAarle,4 T. Kerbusch5 and D. Montgomery4

1Harvard Medical School, Boston, MA, U.S.A.; 2Oregon Medical Research

Center, Portland, OR, U.S.A.; 3SCIderm Research Institute and

Dermatologikum Hamburg, Hamburg, Germany; 4Merck & Co, Inc.,

Kenilworth, NJ, U.S.A. and 5Certara U.S.A., Inc., Princeton, NJ, U.S.A.We evaluated antidrug antibody (ADA) development with til-

drakizumab, an anti-interleukin (IL)-23p19 monoclonal anti-

body in development for psoriasis, in 1400 patients pooled

from three randomized controlled studies: P05495 (phase IIb;

NCT01225731), reSURFACE 1 (phase III; NCT01722331) and

reSURFACE 2 (phase III; NCT01729754). Each study included

tildrakizumab 200-mg and 100-mg doses and had treatment

until week 52 (P05495 and reSURFACE 2) or week 64 (re-

SURFACE 1). Patients with at least one postdose ADA result

were evaluated. The proportions of treatment-emergent-

positive (TE-POS) patients to evaluable patients were reported.

TE-POS patients were further characterized for neutralizing

capacity (NAb-POS). The proportions of TE-POS patients were

4.3% (100 mg) and 4.1% (200 mg) through 12–16 weeks

(primary end points) and 6.5% (100 mg) and 8.2%

(200 mg) through 52–64 weeks. The proportions of TE-POS/

NAb-POS were 0.6% for both doses through 12–16 weeks

and were 2.5% (100 mg) and 3.2% (200 mg) through 52–64 weeks. The proportion of inconclusive patients through

52–64 weeks was low (< 7%), hence most of the remaining

dataset was reliable for interpretation. Patients in the TE-POS/

NAb-POS category showed decreased tildrakizumab concentra-

tions, and a modest increase in median clearance (36.5%) vs.

ADA-negative patients. The proportions of TE-POS (NAb-POS

and NAb-NEG) patients vs. negative/inconclusive patients

achieving ≥ 75% improvement in Psoriasis Area and Severity

Index (PASI 75) at week 12 were 60% vs. 63% (100 mg) and

69% vs. 65% (200 mg); for PGA clear or minimal at week 12

they were 57% vs. 58% (100 mg) and 66% vs. 60%

(200 mg). When the subgroup of TE-POS NAb-POS patients

was isolated and compared with ADA-negative patients

through week 12, percentage PASI improvements were 62%

(n = 4) vs. 75% (n = 603) for 100 mg and 38% (n = 4) vs.

76% (n = 374) for 200 mg. For patients on 100 mg or

200 mg continuously through week 52, the subgroup of TE-

POS NAb-POS patients was compared with ADA-negative

patients. This subgroup showed lower percentage improve-

ments vs. ADA-negative patients: 76% (n = 10) vs. 91%

(n = 342) for 100 mg and 77% (n = 12) vs. 87% (n = 299)

for 200 mg. Clinical responses in other ADA-positive cate-

gories and inconclusive patients were similar to those in nega-

tive patients. The incidences of adverse events and serious

adverse events were similar in the TE-POS and negative/incon-

clusive groups. In summary, ADA development in patients on





from gene to clinic

77ABSTRACTS

tildrakizumab over 52 weeks was low and had a minimal

impact on efficacy and safety.

P005Next-generation sequencing identifies epidermalmicroRNAs deregulated in psoriasis skinA. Srivastava,1 L. Pasquali,1 F. Meisgen,1

M. Stahle,1,2 N.X. Land�en,1 A. Pivarcsi1 andE. Sonkoly1,21Karolinska Institutet, Stockholm, Sweden and 2Karolinska University

Hospital, Stockholm, SwedenPsoriasis is a common chronic inflammatory skin disease,

which is thought to be a result of aberrant interaction

between keratinocytes and the immune system. MicroRNAs

(miRNAs) are short noncoding RNAs that regulate the expres-

sion of the majority of protein-coding genes. We and others

have previously identified miRNAs deregulated in psoriasis

skin, which regulate keratinocyte and/or immune cell func-

tions. Most of the previous studies utilized full-depth skin

biopsies, which contain a mixture of cells, and thus cell-speci-

fic transcriptomic changes may have been masked by expres-

sion in other cell types. Here we analysed the miRNome of

CD45 (nonimmune) sorted epidermal cells from lesional and

nonlesional skin of patients with psoriasis, and from healthy

skin of control patients by next-generation sequencing (RNA-

seq) of small RNAs. Our results revealed differential expres-

sion of 104 miRNAs in the epidermal cells in psoriasis

lesions, including several known and novel miRNAs that have

not been previously associated with psoriasis. MiR-149 was

identified as one of the significantly downregulated miRNAs,

and quantitative polymerase chain reaction analysis confirmed

its downregulation in psoriatic lesional epidermal cells com-

pared with those from nonlesional or normal skin. In primary

human keratinocytes and in three-dimensional epidermal

equivalents, miR-149 was significantly downregulated by

interferon (IFN)-c. Overexpression of miR-149 suppressed the

IFN-c-induced expression of interleukin-6, as well as T-cell-

attracting chemokines, while inhibition of endogenous mi

R-149 led to increased induction of these mediators. Taken

together, we have characterized the cell-specific miRNome in

epidermal nonimmune cells in psoriatic skin, and identified

epidermal miRNAs previously not associated with psoriasis.

MiR-149 has been identified as a miRNA regulating the

response of keratinocytes to IFN-c. Our results can provide a

basis for further functional studies of miRNAs in keratinocytes,

which might lead to identification of potential targets for topi-

cal therapy in psoriasis.

P006Effect of adipose-derived stem cells on animiquimod-induced psoriasiform mouse model byhypodermic injectionJ. Deng, C. Lu, L. Han and Y. HuangGuangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaOur study objective was to explore the effects of adipose-

derived stem cells (ADSCs) on an imiquimod-induced

psoriasiform mouse model by hypodermic injection. Mice

were topically painted with imiquimod for seven consecutive

days to develop psoriatic skin lesion. Mice in the experimental

group had hypodermic injection of ADSCs at day 3 and day 6,

while the control group were given a hypodermic injection of

normal saline. Various analyses related to lesion severity, ingu-

inal lymph nodes change and cytokines expression of lesions

were carried out. Compared with the control group, the Psori-

asis Area and Severity Index score was reduced in the experi-

mental group. Inguinal lymph nodes as the immune organ

were enlarged due to imiquimod painting in the control

group. However, the size of inguinal lymph nodes trended to

normal after ADSC injection. T helper (Th)1/Th2/Th17

cytokines in lesions were detected by flow cytometry. Com-

pared with the control group, the expressions of interferon-cand tumour necrosis factor-a were decreased after ADSC

injection. ADSC hypodermic injection can alleviate

imiquimod-induced psoriasiform lesions, and may exert

immune regulation effects by direct cell-to-cell contact.

P007Impairment of gustatory and olfactory senses inplaque psoriasisP. R€uter,1 V. Gr€unthaler,1 Y. Zopf2 andM. Sticherling11Hautklinik Universit€atsklinikum Erlangen, Erlangen, Germany and2Medizinische Klinik 1, Universit€atsklinikum Erlangen, Erlangen, GermanyThe various aspects of nutrition are a major issue in patient care

for psoriasis. Metabolic disorders and increased body mass index

are frequently encountered in this patients group and may result

from systemic inflammation characteristic for the disease and/

or unbalanced intake of food calories by the patients. Interest-

ingly, in chronic inflammatory bowel diseases relevant gustatory

and olfactory changes have been detected. These result in a dis-

turbed food intake and are normalized again upon successful

treatment of the disease. Here, patients with psoriasis were

tested before any systemic treatment for the gustatory qualities

sweet, sour, salty, bitter and umami. They were tested with

appropriate solutions sprayed onto the back of the tongue in a

standardized procedure, as well as by using sniffing sticks for

olfaction. Thirty-three patients were tested: 18 women and 15

men with a mean age of 54.3 years (range 21–85), a mean Pso-

riasis Area and Severity Index (PASI) of 8 (range 0.7–24) and

mean C-reactive protein (CRP) of 5.4 ng mL�1 (range 0.6–24.1). The results were compared with those in a group of

healthy volunteers. Whereas sweet taste was detected by all

patients, bitter could not be tasted by 21 patients and umami by

11 patients. Two and 23 patients showed hyposmia with results

off the 10% and 50% percentiles of normal volunteers, respec-

tively. Altogether, a distinct impairment of gustatory and olfac-

tory senses was found in patients with psoriasis. Considering

the low number of patients, the correlation to PASI and CRP was

barely significant. In addition, a normalization of sensory capac-

ity in relation to therapeutic responses and improvement of pso-

riasis has to be monitored.



P008Psoriasis in children: a single-centre analysisF. Heppt, J. Raap and M. SticherlingDepartment of Dermatology, University Hospital of Erlangen, Erlangen,

GermanyEvidence-based guidelines for the treatment of psoriasis in

childhood are still lacking. Although several consensus recom-

mendations have been presented within the last few years,

treatment of paediatric psoriasis remains challenging for der-

matologists and paediatricians. The aim of this study was to

analyse more data regarding epidemiology, clinics, associated

comorbidities and therapeutic strategies. In a monocentric, ret-

rospective analysis over a period of 5 years (2009–2014), allpaediatric patients (age < 18 years) with psoriasis of any type

were evaluated. Diagnosis was usually made by the clinical

appearance and, if necessary, histologically confirmed.

Descriptive statistics were used for analysis. In total 73 patients

were analysed, representing 3.7% of all treated patients with

psoriasis in the analysis period. There was a female predomi-

nance (55%) and the mean age of disease onset was

10.5 years (range 2–17). Forty cases (45%) showed a positive

family history. The most common form was classic plaque

type psoriasis (67%), whereas the guttate form was seen in

30% of the patients. Five patients (7%) had psoriatic arthritis.

Specific topical treatments included corticosteroids (81%),

vitamin D analogues (73%), dithranol (32%) and calcineurin

inhibitors (8%). Fourteen patients received phototherapy and

systemic treatment was given in nine cases. Concerning the

most common comorbidities, six patients (8%) showed symp-

toms of a depressive mood. In addition, five children (7%)

were identified who had arterial hypertension and another five

were obese. In conclusion, regarding the high rate of comor-

bidities in our study population, screening for and manage-

ment of these comorbidities in this young and sensitive

population are of prime importance, especially concerning

long-term follow-up. International evidence-based guidelines

for the treatment of childhood psoriasis are highly desirable.

P009Interleukin-36c detection via noninvasive tapestripping reliably diagnoses psoriasisA. Keszegpal,1 A. Latzko,1 G. Brown,2 M. Goodfield,3

P. Laws,3 T. Macleod,4 J. Ainscough,4 A. Alase,1

D. Reid,2 J. Wenzel,5 P. Helliwell,1 M. Stacey4 andM. Wittmann1

1University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal

Medicine, Leeds, U.K.; 2University of Aberdeen, MRC Centre for Medical

Mycology, Aberdeen, U.K.; 3Department of Dermatology, Leeds, U.K.;4University of Leeds, School of Cellular and Molecular Biology, Leeds, U.K.

and 5University of Bonn, Department of Dermatology, Bonn, GermanyPsoriasis is a common skin disease that presents with a variety

of clinical phenotypes. In certain anatomical locations (e.g.

palmoplantar, auricular, intertriginous) or in cases of minimal

clinical activity, diagnosis can be problematic. In primary care

settings some psoriasis subtypes can be misdiagnosed as

eczema or other skin conditions. This study aimed to develop

a simple, reliable diagnostic tool for psoriatic inflammation.

Our approach was to use a noninvasive tape-stripping

methodology and enzyme-linked immunosorbent assay

(ELISA)-based measurement of cytokines including an in-

house-developed ELISA for interleukin (IL)-36c. Epidermal

cytokines from skin of healthy individuals were compared

with skin lesions typical for psoriasis or atopic dermatitis. We

here demonstrate that IL-36c is a highly sensitive and selective

protein biomarker that distinguishes psoriasis from eczema

lesions and is superior to other proteins upregulated in psori-

atic epidermis including IL-8, IL-18 and CXCL1. Receiver

operating characteristic curve analysis showed 90.6% sensitiv-

ity and 100% specificity at a cut-off level of 540 pg IL-36clg�1 total protein. In clinically ambiguous skin lesions requir-

ing diagnostic biopsies, IL-36c also proved to diagnose psori-

atic inflammation accurately. Epidermal markers that have

previously been linked to atopic eczema, including thymic

stromal lymphopoietin and CCL17, failed to show a robust

diagnostic potential in this approach. We conclude that pro-

tein sampling and detection of IL-36c via noninvasive tape-

stripping allows reliable diagnosis of psoriasis. This diagnos-

tic could improve patients’ outcomes by avoiding inappro-

priate treatment such as topical or systemic antibiotics,

which are often seen in primary care settings where lesions

may be confused with eczema. Correct identification of skin

psoriasis will facilitate early diagnosis of psoriatic arthritis

and prevention strategies for other psoriasis-associated

comorbidities.

P010Caffeine in the treatment of atopic dermatitis andpsoriasis: a reviewM. Alashqar1 and N. Goldstein21Alfaisal University, Riyadh, Saudi Arabia and 2Mount Sinai Health System,

New York, NY, U.S.A.Atopic dermatitis (AD) and psoriasis are inflammatory skin

diseases. AD is characterized by immune dysregulation and

barrier impairment, while psoriasis shows immune dysfunc-

tion and resultant keratinocyte hyperproliferation. Caffeine has

shown efficacy in ameliorating the symptoms of both diseases,

but it is not conclusive through which pathways. The aim of

this study was to provide a detailed discussion of the available

work on this topic, as well as known modes of action of caf-

feine that are relevant to these two conditions. After an exten-

sive review of the literature, we found that both diseases have

decreased intracellular cAMP levels in cutaneous leucocytes, so

it is very likely that being a methylxanthine, and hence a

phosphodiesterase inhibitor, caffeine raises intracellular cAMP

levels, which suppresses inflammatory pathways and potenti-

ates anti-inflammatory ones. Moreover, caffeine is known to

be an ATR (ataxia-telangiectasia mutated) kinase inhibitor and

an ATM (ATM- and Rad3-related) kinase inhibitor, which pro-

motes prompt apoptosis of damaged cells. It was also found

to have antinecrotic effects in cells damaged by reactive oxy-

gen species (ROS). These proapoptotic and antinecrotic prop-

erties may also be reducing the inflammation. Finally,





from gene to clinic

79ABSTRACTS

caffeine’s metabolites have shown antioxidizing effects against

ROS, which certainly would reduce inflammation caused by

lipid peroxidation, DNA damage and organelle destruction.

We find that caffeine acts in a number of ways to improve

symptoms of inflammation and that it is an effective adjunct

to therapy in AD and psoriasis.

P011Population pharmacokinetic modelling oftildrakizumab (MK-3222), an anti-interleukin-23-p19 monoclonal antibody, in healthy volunteersand patients with psoriasisP. Jauslin,1 P. Kulkarni,1 R. Wada,1 S. VataKuti,1

A. Hussain,2 L. Wenning2 and T. Kerbusch11Certara U.S.A., Inc., Princeton, NJ, U.S.A. and 2Merck & Co., Inc.,

Kenilworth, NJ, U.S.A.Tildrakizumab is an anti-interleukin (IL)-23p19 monoclonal

antibody in development for the treatment of chronic plaque

psoriasis. In this analysis, we characterize the population phar-

macokinetics (PK) of tildrakizumab and identify covariates

influencing its exposure. A population PK model was devel-

oped using six studies conducted in 2098 healthy volunteers

and patients with psoriasis. The model was found to be robust

and predictive using a nonparametric bootstrap and predic-

tion-corrected visual predictive check, respectively. Covariates

of interest included body weight, formulation type, sex, age,

race, serum albumin and ethnicity. The PK were described by

a one-compartment model with first-order absorption and

elimination kinetics, and interindividual variability on clear-

ance, volume of distribution and absorption rate constant. The

PK of tildrakizumab were characterized by low clearance and

limited volume of distribution. In patients with psoriasis, the

geometric mean clearance was 0.32 L per day (38%), the vol-

ume of distribution was 10.8 L (24%), and the absorption

and elimination half-lives were 1.5 days (18%) and 23.4 days

(23%), respectively, with an absorption lag time of 0.05 days

(1.2 h). For the 100-mg dose, the steady state area under the

curve0–tau and Cmax were 305 lg day mL�1 (41%) and 8.1 lgmL�1 (34%), respectively. The corresponding values for the

200-mg dose were 612 lg day mL�1 (40%) and 16.3 lgmL�1 (33%), respectively. For both doses, Tmax was 6.2 days

(46%). Steady state is achieved by 16 weeks with the clinical

regimen (dosing on weeks 0 and 4 and every 12 weeks there-

after), with 1.1-fold accumulation in Cmax. Healthy patients

had 31% higher bioavailability than those with psoriasis.

Patients with increased bodyweight had lower areas under the

curve than those with lower bodyweight. Clinical comparabil-

ity was defined by the observation that no marked differences

in efficacy (Psoriasis Area and Severity Index response) and

safety (adverse events) were seen in exposure split by quartile

for 100 mg and 200 mg. Thus, bounds were defined by the

median exposure of the extreme quartiles. All covariate effects

(intrinsic and extrinsic factors) resulted in exposures contained

within the clinical comparability bounds for all covariates

including bodyweight. These population PK findings indicate

that the PK for tildrakizumab behave like those of a typical

monoclonal antibody. Based on PK data only, there is no need

for dosage adjustment for these intrinsic and extrinsic factors.

Nonetheless, bodyweight was influential and was subsequently

evaluated in a PK–pharmacodynamics model.

P012

Poster withdrawn.

P013Immune modulation by topical PH-10 aqueoushydrogel (rose Bengal disodium) in psoriasislesionsJ.G. Krueger,1 S. Garcet,1 J. Fuentes-Duculan,2

N. Kunjravia,1 I. Cueto,1 X. Li,1 J.M. Singer3 andE.A. Wachter31Rockefeller University, New York, NY, U.S.A., 2Rockefeller University, New

York, Sint Maarten (Dutch part), NY, U.S.A. and 3Provectus

Biopharmaceuticals, Knoxville, TN, U.S.A.PH-10 is topical hydrogel formulation that yields selective

delivery of rose Bengal disodium (RB) to epithelial tissues. RB

is a fluorescein derivative capable of producing singlet oxygen

upon photoactivation, but its therapeutic mechanism in psori-

asis vulgaris is not established. We thus conducted a mecha-

nistically focused study of PH-10 in 30 patients with psoriasis

vulgaris using sequential vehicle and active drug treatment for

4 weeks each (registered clinical trial NCT02322086). Skin

biopsies were collected before treatment and at the end of

each treatment period. Effects of placebo vs. active treatment

were assessed on cellular immune infiltrates, driver cytokines

of psoriasis and the overall disease transcriptome using

immunohistochemistry and gene-expression profiling with

Affymetrix U133 2.0Plus arrays and reverse-transcriptase poly-

merase chain reaction (RT-PCR). Vehicle treatment for

4 weeks did not significantly alter expression of core inter-

leukin (IL)-23/IL-17-modulated genes or the overall disease

transcriptome (using a principle component analysis, PCA).

However, 4 weeks of treatment with PH-10 significantly (fold

change > 1.5, P < 0.05) downregulated IL-17A, IL-22, IL-26,

IL-36, and keratin 16 mRNAs as assessed by RT-PCR, while a

PCA analysis of the gene array results showed a shift towards

nonlesional skin with some post-treatment biopsies clustering

within the nonlesional skin profile. Pathways that were signifi-

cantly improved by PH-10 included published psoriasis tran-

scriptomes and cellular responses mediated by IL-17, IL-22

and interferons. To strengthen the analysis of immune- and

psoriasis-related gene modulation by PH-10, we divided

patients into responders vs. nonresponders based on the PCA

analysis after 4 weeks of treatment (comparing to nonlesional

skin at baseline). Using this approach, more than 500 disease-

related genes were downregulated during 4 weeks of treat-

ment with PH-10, and expressions of a wide range of central

‘psoriasis related’ genes including IL-23, IL-17, IL-22,

S100A7, IL-19, IL-36 and CXCL1 were effectively normalized;

treated lesional skin had values in the same range as baseline

nonlesional skin. We also measured decreased expression of



T-cell activation markers including ICOS and CTLA4, changes

that were paralleled by decreases in myeloid (CD11c+) den-

dritic cells and T cells using immunohistochemical measures.

The results of this study establish that PH-10 has highly sig-

nificant ability to modulate psoriatic inflammation, including

key cytokine drivers of this disease, but only a subset of

patients revert from the lesional phenotype to that of nonle-

sional skin. This type of ‘mixed’ response outcome occurs

with other topical or systemic drugs now approved for psoria-

sis, highlighting a need to personalize treatments and poten-

tially to have predictive response biomarkers for individual

drugs.

P014Favourable safety profile of ixekizumab: resultsfrom 11 moderate-to-severe psoriasis and threepsoriatic arthritis clinical trialsA. Gottlieb,1 K. Papp,2 W. Xu,3 L. Mallbris3 andN. Agada31Department of Dermatology, New York Medical College, Metropolitan

Hospital New York, NY, U.S.A.; 2Probity Medical Research, Waterloo, ON,

Canada and 3Eli Lilly and Company, Indianapolis, IN, U.S.A.Ixekizumab (IXE) is a high affinity anti-interleukin (IL)-17A

monoclonal antibody. The objective of this report is to pro-

vide an overview of safety from IXE clinical trials in psoriasis

and psoriatic arthritis (PsA). Study results for psoriasis and PsA

have been published separately. IXE psoriasis safety data were

integrated from 11 controlled and uncontrolled clinical trials

in patients with moderate-to severe plaque psoriasis, including

the phase III trials UNCOVER-1, -2 and -3. Integrated IXE PsA

safety data were from three controlled and uncontrolled clini-

cal trials in patients with active PsA, including the phase III

trials SPIRIT-P1 and -P2. Frequencies of treatment-emergent

adverse events (TEAEs) and adverse events of special interest

(AESI) are provided here. Exposure-adjusted incidence rates

(IRs) of AESIs were summarized. The IR is expressed as the

number of unique patients with a particular AESI per 100

patient-years (PY), using the entire duration of exposure dur-

ing treatment period. The 95% confidence interval of the IR

was calculated based on the Poisson regression model with

treatment as the explanatory variable. Major adverse cerebro-

cardiovascular events were adjudicated by an external adjudi-

cation committee. A total of 5689 patients (12061.5 PY) with

psoriasis and 1118 patients (1373.4 PY) with PsA were

exposed to IXE. TEAEs, mostly mild or moderate, were

reported by 4775 (83.9%) patients with psoriasis and by 868

(77.6%) patients with PsA. Injection-site reactions, mostly

mild or moderate, were reported by 840 (14.8%) patients

with psoriasis and by 227 (20.3%) patients with PsA, and

rarely resulted in study drug discontinuation. The IRs of injec-

tion-site reactions decreased substantially over time in both

patients with psoriasis and those with PsA. Serious adverse

events occurred among 670 (11.8%) and 91 (8.1%) patients

with psoriasis and PsA, respectively. Adverse events leading to

discontinuation of study drug occurred among 379 (6.7%)

patients with psoriasis and 80 (7.2%) patients with PsA. There

were 23 (0.4%) deaths among patients with psoriasis and two

(0.2%) deaths among patients with PsA. Most deaths resulted

from cardiovascular events in those with a history of risk fac-

tors, and none was attributed to the study drug. The present

report supports a favourable safety profile of ixekizumab in

different patient populations, those with moderate-to-severe

psoriasis and those with active PsA. This study was funded by

Eli Lilly and Company, Indianapolis, IN, U.S.A.

P015

Poster withdrawn.

P016Cytokine effects of apremilast as a mechanism ofefficacy in systemic-naive patients with moderateplaque psoriasis: results from the UNVEIL trialB. Strober,1,2 M. Alikhan,3 B. Lockshin4 andP. Schafer51University of Connecticut, Farmington, CT, U.S.A.; 2Probity Medical

Research, Waterloo, ON, Canada; 3University of Cincinnati Medical Center,

Health Dermatology, Cincinnati, OH, U.S.A.; 4DermAssociates, Silver Spring,

MD, U.S.A. and 5Celgene Corporation, Summit, NJ, U.S.A.Previous pharmacodynamic (PD) subanalyses of clinical trials

have demonstrated that the effects of apremilast on key cyto-

kines involved in the pathogenesis of plaque psoriasis play a

role in determining clinical efficacy. It was therefore of inter-

est to perform a more detailed PD substudy of a phase IV ran-

domized, controlled trial (UNVEIL), which evaluated the

efficacy and safety of apremilast 30 mg twice daily (APR) in

the treatment of systemic-naive patients with moderate plaque

psoriasis [psoriasis-involved body surface area (BSA) 5%,10%;

static Physician’s Global Assessment = 3 (moderate)]. Patients

were randomized (2 : 1) to APR or placebo (PBO) for

16 weeks. From the PD patient subset, blood samples obtained

at weeks 0 (baseline), 4 and 16 were analysed for interleukin

(IL)-17A, IL-17F, IL-22, IL-23; leptin; adiponectin;

apolipoproteins A-I, A-II, B and E; and numbers of circulating

T helper 17 (Th17) cells, regulatory T cells (Tregs) and total

T-cell numbers. Correlations were examined between percent-

age change from baseline in key inflammatory biomarkers and

clinical efficacy, based on assessments using the product of the

sPGA and psoriasis-involved BSA (PGA 9 BSA). Of the total

221 patients randomized into the phase IV trial, the PD sub-

population included 38 patients (APR, n = 26; PBO, n = 12).

At week 4, the median percentage changes from baseline in

IL-17A, IL-17F, IL-22 and IL-23 with APR vs. PBO were

�42.5% vs. 9.3% (P= 0.019), �64.4% vs. 12.8% (P<

0.001), �42.9% vs. 8.6% (P= 0.0021) and �15.2% vs.

�6.6% (P = 0.69). At week 16, percentage change in IL-17A

significantly correlated with percentage change (improvement)

in PGA 9 BSA (r = 0.45, P= 0.04). At weeks 4 and 16, levels

of leptin, adiponectin and apolipoproteins A-I, A-II, B and E,

as well as numbers of circulating Th17 cells, Tregs, and total

T cells, were largely unchanged from baseline. Improvements

in clinical signs and symptoms of psoriasis at week 16, based





from gene to clinic

81ABSTRACTS

on PGA 9 BSA, correlated with apremilast-mediated decreases

in IL-17A without affecting upstream systemic IL-23 levels

and without affecting the number of Th17 cells or Tregs.

Apremilast had no effect on adipokines or apolipoproteins.

This study was funded by Celgene Corporation.

P017Patient- and physician-reported outcomes withapremilast for patients with plaque psoriasisduring routine dermatology care in Germany:an interim analysisK. Reich,1 S. Bomas,2 B. Korge,3 M. Manasterski,4

U. Schwichtenberg,5 H. Mentz,6 K. Groegel6 andN. N�unez G�omez6

1SCIderm Research Institute and Dermatologikum Hamburg, Hamburg,

Germany; 2Praxis Dr. med. S. Rotterdam, Gelsenkirchen-Feldmark, Germany;3Priv. Doz. Dr. med. Korge, D€uren, Germany; 4Hautarztpraxis Manasterski

und Dues, Berlin, Germany; 5Derma Nord Hautarztpraxen Dr. med.

Schwichtenberg, Bremen, Germany and 6Celgene GmbH, Munich, GermanyLAPIS-PSO (ClinicalTrials.gov NCT02626793) is an ongoing,

52-week, prospective, multicentre, noninterventional, observa-

tional cohort study in real-world dermatology clinical settings

in Germany. LAPIS-PSO is evaluating patient- and physician-

reported outcomes of quality of life, treatment satisfaction and

treatment effectiveness in patients with psoriasis during long-

term apremilast therapy. The primary end point is the propor-

tion of patients who achieve a Dermatology Life Quality Index

(DLQI) score ≤ 5 or an improvement in the DLQI score by ≥ 5

points from baseline. Presented here is a 4-month interim

analysis of patient-reported outcomes and efficacy assessments

of apremilast among enrolled patients (n = 111; full analysis

set, n = 73) who were continuing apremilast therapy at

4 months. At baseline, the mean age was 50.9 � 13.2 years

in the full analysis set, and 38 patients (52%) are female. At

the time of apremilast initiation, 63 patients (86%) had Physi-

cian’s Global Assessment (PGA) of disease severity ≥ 3; the

mean psoriasis-involved body surface area (BSA) was 22.9%,

the mean pruritus visual analogue scale (VAS) score was

57.8 mm, and the mean DLQI score was 14.6. Among

patients who were continuing apremilast therapy at 4 months,

a total of 41 of 64 patients (64%) achieved the primary end

point of either DLQI ≤ 5 or DLQI reduction ≥ 5. Mean per-

centage improvements were observed for BSA

(�10.3 � 14.7) and pruritus VAS (�48.0%); 27% of patients

achieved a PGA rating of 0 (clear) or 1 (minimal), and 31%

had a PGA rating of 0 or 1. Post hoc Spearman correlation

analyses showed that reductions from baseline in pruritus VAS

score were highly correlated with reduction in scalp psoriasis

severity (r = 0.59) and improvement in DLQI score

(r = 0.68). Responses on the Systemic Therapy Adherence

Questionnaire (STAQ) showed that most patients (> 50%)

who were continuing apremilast therapy at month 4 agreed or

strongly agreed that they were satisfied with apremilast tolera-

bility, would continue with apremilast therapy, and would

recommend it to other patients. Substantial proportions indi-

cated satisfaction with apremilast efficacy (49%) and onset of

effect (47%); 42% indicated that their therapeutic goals had

been met. A total of 27 patients (25%) reported at least one

adverse event (AE). There was one AE that occurred in ≥ 5%

of patients (diarrhoea, n = 9, 8%). AEs were consistent with

the known safety profile of apremilast. In clinical routine care

in Germany, outcomes of apremilast treatment for patients

with psoriasis were comparable with results from apremilast

clinical trials. This study was funded by Celgene Corporation.

P018Shear wave elastography in patients on high-dosemethotrexate: a prospective studyD. Kivelevitch,1 R. Rahimi2 and A. Menter11Division of Dermatology and 2Transplant Hepatology, Baylor Scott & White,

Dallas, TX, U.S.A.Long-term methotrexate (MTX) use in the psoriasis population

may be associated with liver fibrosis. Multidisciplinary special-

ists and society guidelines differ in their approaches for estab-

lishing liver fibrosis. We examined the role of noninvasive

assessment of fibrosis using ultrasound-based shear wave elas-

tography (SWE) in patients predominantly with psoriasis and

rheumatoid arthritis on long-term MTX treatment. In this

prospective study, 91 patients on high-dose MTX were evalu-

ated using SWE. Fibrosis stage was defined as: 6–7.9 kPa

(stage 1); 8–9.9 kPa (stage 2); 10–11.9 kPa (stage 3) or ≥12 kPa (stage 4 or early cirrhosis). In a subset, liver stiffness

(in kPa) was correlated with fibrosis stage on liver biopsy

based on the results of SWE and risk factors for metabolic syn-

drome. Between January 2014 and May 2016, 91 patients

were enrolled: mean age 61 years, 76% female; 59% with

psoriasis (52 patients), 30% rheumatoid arthritis (26 patients)

and 11% other (seven patients); mean body mass index (BMI)

32.1 � 7.9 kg m�2; on a mean high cumulative MTX dose of

5374 � 3391 mg. Nonalcoholic fatty liver disease (based on

imaging or history) and diabetes were seen in 38 (42%) and

19 (21%) patients, respectively. Six patients were excluded

due to missing data. Eighty-one per cent underwent SWE and

38% underwent concomitant liver biopsy. Overall 82% had an

abnormal result suggesting presence of fibrosis (METAVIR

score ≥ F1); the incomplete or unreliable rate was 7% (n = 6)

seen in patients with morbid obesity (BMI 37 kg m�2). The

mean stiffness was 9.7 � 4.8 kPa, suggestive of stage 2 fibro-

sis. Twelve per cent had stiffness > 12 kPa; however, liver

biopsy did not show any cirrhosis, but rather stage 0 (n = 3),

stage 1 (n = 6) and stage 3 (n = 2) were represented. None

of the patients with normal stiffness or a value ≤ 12 kPa had

cirrhosis on biopsy. Being obese increased the likelihood of

obtaining any abnormal SWE result compared with overweight

patients (P = 0.049). Mean platelets, total bilirubin, alkaline

phosphatase, aspartate aminotransferase, alanine aminotrans-

ferase and international normalized ratio did not differ

between those receiving liver biopsy and those assessed with

SWE alone. In patients on high cumulative doses of MTX,

SWE overestimated the presence of advanced fibrosis, specifi-

cally in obese patients. Furthermore, the negative predictive

value for absence of advanced fibrosis was high, suggesting



that SWE is helpful for screening out patients who do not

have advanced fibrosis. The role of serial SWE in patients with

psoriasis using MTX is currently being evaluated.

P019Do patients with certain human leucocyte antigenexpression have a higher risk of developingpsoriasis?A. Anandan, K. Radhakrishnan, R. Prasada andV.K. PanickerSri Ramachandra University, Chennai, IndiaPsoriasis is an immune-mediated genetically determined skin

disorder affecting 1–3% of people worldwide. Psoriasis is a

multifactorial disease and has been associated with certain

human leucocyte antigen (HLA) expressions. This study is

focused on HLA association in psoriasis by screening patients

with psoriasis for HLA class I and determining its odds ratio

(OR). The study was conducted at the department of trans-

fusion medicine at a tertiary-care hospital. In total 100

patients with psoriasis (cases) and 100 controls (healthy blood

donors) were enrolled in the study. Samples from the patients

with psoriasis were collected from dermatology outpatient

department and the samples from the controls were taken

from voluntary blood donors at the department of transfusion

medicine after obtaining consent. HLA typing for class I was

done using the single specific primer polymerase chain reac-

tion method. The HLA results were statistically analysed and

the association with psoriasis was determined. The alleles that

were found in higher frequency among the cases were HLA-

A*02 (45%, OR 2.33) and HLA-A*24 (35%, OR 2.15). HLA-

B*35 (36%, OR 2.40) was observed at a higher frequency

among the cases. HLA-C*06 and HLA-C*07 were found in 52%

and 33% of samples and had ORs of 9.75 and 2.06, respec-

tively among the patients. Certain HLA alleles are present in

higher frequency in the disease population than in the con-

trols, implying that individuals expressing these alleles may

have a higher relative risk of developing psoriasis.

P020Utility study to map utilities to the Psoriasis Areaand Severity Index and Dermatology Life QualityIndex instruments in patients with chronic plaquepsoriasisC. Baker,1,2 J. Sullivan,3 P. Davey4 and J. Wilson5

1Skin and Cancer Foundation Inc., Melbourne, Australia; 2St Vincent’s

Hospital, Melbourne, Australia; 3Holdsworth House Dermatology, Sydney,

Australia; 4Illuminate Health Consulting, Sydney, Australia and 5AbbVie,

Sydney, AustraliaNational funding bodies such as the U.K. NICE, Scotland’s

SMC and Australia’s PBAC have a preference for cost utility

analyses to determine cost-effectiveness when making deci-

sions regarding funding of new treatments. No published

studies currently exist that allow the Psoriasis Area and Sever-

ity Index (PASI) or Dermatology Life Quality Index (DLQI)

instruments to be validly converted to utilities. The purpose of

the study was to generate utility weights that correspond to

the full range of scores from the PASI and DLQI. Study partici-

pants (total 74) were from two psoriasis treatment clinics in

Australia. Patient information for the utility instruments was

collected in face-to-face interviews. Informed consent was

obtained and the study approved by a local ethics committee.

To assess the relationship between the PASI and DLQI instru-

ments and utilities, curve-fitting procedures were performed.

The proportion of variance or multiple correlation coefficients

(R2) that could be explained by the model were indicated by

a goodness of fit. The curves explored include linear, squared,

cubic, polynomial, logarithmic and square root. Subgroups

were selected for stratification to ensure that there were suffi-

cient data points across the range of PASI scores (0–72). Thedata were sampled into subgroups according to the following

PASI scores: 0–3, 3–10, 10–15 and 15–72. Three instruments

were administered during the full study: two disease-specific

instruments measuring psoriasis severity, the PASI and the

DLQI, and a general quality-of-life (QoL) instrument measur-

ing patient utility, the EuroQol-5D (EQ-5D). The DLQI is a

disease-specific QoL instrument with higher scores indicating

a more impaired quality of life. In contrast the EQ-5D mea-

sures health states on a 0–1 scale where higher scores reflect

an improved health state. A number of patient responses were

excluded based on illogical or incomplete responses, leaving

56 patient responses for analysis. The correlations between

EQ-5D and PASI and EQ-5D and DLQI were highly significant

(P < 0.001), with negative coefficients. Furthermore, the asso-

ciation between EQ-5D and DLQI appears to be stronger than

that between EQ-5D and PASI. In conclusion, EQ-5D utility

decreases when the PASI or DLQI score increases, meaning

that as symptoms increase patients report poorer quality of

life. The results from this study were consistent with two pre-

vious studies that attempted to map utilities to psoriasis symp-

toms, with a square-root predictive model showing no

substantial difference.

P021Secukinumab shows high and sustained efficacy innail psoriasis: 2.5-year results from theTRANSFIGURE studyK. Reich,1 P. Arenberger,2 U. Mrowietz,3 S. Jazayeri,4

M. Augustin,5 A. Parneix,6 P. Regnault,7 R. You8 andJ. Frueh71Dermatologikum Hamburg and SCIderm Research Institute, Hamburg,

Germany; 2Department of Dermatology, Charles University, Prague, Czech

Republic; 3Psoriasis Center at the Department of Dermatology, University

Medical Center Schleswig-Holstein, Kiel, Germany; 4Alliance Dermatology and

MOHS Center, Phoenix, AZ, U.S.A.; 5Universit€at Hamburg, Hamburg,

Germany; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, U.S.A.;7Novartis Pharma AG, Basel, Switzerland and 8China Novartis Institutes for

BioMedical Research, Shanghai, ChinaNail psoriasis is associated with decreased finger mobility,

functional impairment, pain and reduced quality of life and is

often difficult to treat. It correlates with more severe psoriatic

disease and is an important predictor of psoriatic arthritis

(PsA). Nails are affected in up to 50% of patients with





from gene to clinic

83ABSTRACTS

psoriasis, with a lifetime incidence as high as 90%. Secuk-

inumab, a fully human monoclonal antibody that selectively

neutralizes interleukin-17A, has demonstrated significant effi-

cacy in the treatment of moderate-to-severe psoriasis and PsA,

demonstrating a rapid onset of action and sustained responses

with a favourable safety profile. Here we report the long-term

follow-up efficacy and safety results from the TRANSFIGURE

study, the first robust (2.5-year) data reported in patients with

nail psoriasis treated with secukinumab. TRANSFIGURE is a

double-blind, randomized, placebo-controlled, parallel-group,

multicentre phase IIIb study to investigate the safety and effi-

cacy of secukinumab 150 and 300 mg subcutaneous in mod-

erate-to-severe nail psoriasis, involving 198 patients. As

previously reported, at week 16 the primary end point NAPSI

(Nail Psoriasis Severity Index) and all secondary end points of

this study were met, demonstrating superiority of secuk-

inumab over placebo after 16 weeks of placebo-controlled

treatment.2 An interim analysis at week 80 demonstrated the

continuation of improvement in nail psoriasis for all efficacy

parameters. The effect was sustained through 2.5 years with

large mean NAPSI improvements from baseline of �73.3%

and �63.6% with secukinumab 300 mg and 150 mg, respec-

tively (as observed). Secukinumab demonstrated sustained

reductions (improvements) in total mean NAPPA (Nail Assess-

ment in Psoriasis and Psoriatic Arthritis) quality-of-life scores

from baseline to 2.5 years by �52.4% (300 mg) and �18.1%

(150 mg), and 70.2% (300 mg) and 71.0% (150 mg) of

patients achieved a weighted NAPPA-Patient Benefit Index glo-

bal score of ≥ 2 (at least moderate benefits) (last observation

carried forward). Patients showed considerable improvements

in EQ-5D (EuroQoL 5-Dimension Health Status Questionnaire)

compared with baseline, reporting decreased pain and discom-

fort. The safety profile was consistent with that observed in

previous phase III trials of psoriasis and PsA. TRANSFIGURE is

the first large, randomized controlled trial to report long-term

results in patients with nail psoriasis. Secukinumab demon-

strated strong sustainability of clinically meaningful efficacy,

large quality-of-life improvement and a favourable safety pro-

file up to 2.5 years in difficult-to-treat nail psoriasis. This

investigation was sponsored by Novartis Pharma AG, Basel,

Switzerland.

P022Secukinumab pooled and long-term safety:analysis of 19 psoriasis clinical trialsP. van de Kerkhof,1 K. Reich,2 C. Leonardi,3

A. Blauvelt,4 N. Mehta,5 T.-F. Tsai,6 R. You,7

P. Papanastasiou,8 M. Milutinovic8 andC.E.M. Griffiths91Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands;2Dermatologikum Hamburg and Georg-August-University, G€ottingen,

Germany; 3Saint Louis University Health Sciences Center, St Louis, MO,

U.S.A.; 4Oregon Medical Research Center, Portland, OR, U.S.A.; 5National

Heart, Lung, and Blood Institute, Bethesda, MD, U.S.A.; 6National Taiwan

University College of Medicine, Taipei, Taiwan; 7China Novartis Institutes

for BioMedical Research, Shanghai, China; 8Novartis Pharma AG, Basel,

Switzerland and 9University of Manchester, Manchester, U.K.We report exposure adjusted incidence rates (IRs) for treat-

ment-emergent adverse events per year from a pooled analysis

of all secukinumab psoriasis trials to date (19 studies, 4674

Year 1 Year 2 Year 3 Year 4 Year 5Secukinumab ETN UST PBO Secukinumab Secukinumab Secukinumab Secukinumab

Dose (mg) Any 300 50 45/90 Any 300 Any 300 Any 300 Any 300Patients 4676 1773 323 336 1090 3423 1188 1972 572 1522 397 909 263

Exposure(patient-years)

4093.5 1467.4 296.9 318.1 301.2 2631.3 859.6 1659.6 423.0 1392.2 377.5 291.6 90.0

Any AEs 254.1 275.6 245.7 252.2 355.8 169.9 168.1 159.8 160.2 104.1 111.9 12.0 13.9Frequent AEs

Nasopharyngitis 27.4 28.4 35.9 31.2 35.9 22.7 21.2 23.2 24.1 14.4 11.8 1.0 3.4Headache 10.5 12.6 15 14.6 23.7 5.1 5.4 4.8 4.3 3.4 4.9 0.0 0.0

URTI 8.8 9.1 5.9 9.9 8.8 7.2 7.3 6.9 6.1 5.2 5.5 0.0 0.0Selected AEs

Opportunisticinfections

0.2 0.2 0.3 0.3 0.3 0.1 0.1 0.0 0.0 0.1 0.0 0.0 0.0

Candida infections 3.1 4.7 1.4 1.6 1.7 2.0 3.6 1.4 1.9 1.5 1.3 0.3 1.1Neutropenia 0.5 0.5 1.4 0.0 0.0 0.3 0.1 0.2 0.0 0.1 0.0 0.0 0.0

MACE 0.4 0.5 0.3 0.3 1.3 0.1 0.1 0.3 0.5 0.4 0.0 0.0 0.0Crohn disease 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

Ulcerative colitis 0.2 0.1 0.3 0.0 0.0 0.2 0.4 0.1 0.2 0.1 0.3 0.0 0.0Malignant or

unspecified

tumours(except

NMSC)

0.5 0.4 0.3 0.3 0.3 0.3 0.4 0.5 0.2 0.2 0.0 0.0 0.0



patients, 10 061 patient-years of exposure). Adverse event

(AE) IRs (per 100 patient-years) were examined per year for

patients who received either secukinumab 300 mg or any

dose of secukinumab, and, for 1 year only, for patients receiv-

ing placebo (PBO), etanercept (ETN) 50 mg or ustekinumab

(UST) 45/90 mg. The pooled safety of secukinumab remained

favourable over 5 years of treatment with no increase of AEs

over time. Additionally, secukinumab demonstrated a compa-

rable pooled safety profile to that of PBO, ETN and UST over

the course of 1 year (see Table; MACE, major adverse cardio-

vascular event; NMSC, nonmelanoma skin cancer; URTI, upper

respiratory tract infection). This comprehensive pooled analy-

sis supports the favourable long-term safety profile of secuk-

inumab in patients with psoriasis. This investigation was

sponsored by Novartis Pharma AG, Basel, Switzerland.

P023Lysosomal action in the regulation of inflammatoryprocesses on the example of psoriasisK. Boche�nska,1 M. Moskot,2 E. Smoli�nska,1

J.J.-Banecka1 and M. Gabig-Cimi�nska21Department of Medical Biology and Genetics, University of Gda�nsk, Gda�nsk,

Poland and 2Institute of Biochemistry and Biophysics, Polish Academy of

Sciences, Laboratory of Molecular Biology (affiliated with the University of

Gda�nsk), Gda�nsk, PolandChronic inflammation is strongly associated with the patho-

genesis of many dermatological diseases, including psoriasis.

Despite the ever-growing knowledge of the causes and devel-

opment of abnormal immune responses, factors involved in

these processes are still being sought. The main goal of the

following research is clarification the role of lysosomes in the

development of inflammation and results obtained regarding

correlation with calcium ion levels and calcineurin activity at

later stages. Studies are carried out on three models: (i) in vitro

‘psoriasis-like’ activated HaCaT cells, (ii) in vitro keratinocytes

derived from patient tissue (from lesional and nonlesional

psoriatic skin and normal skin as a control), and (iii) ex vivo

directly on skin tissue biopsies (from lesional and nonlesional

psoriatic skin and normal skin as a control). Preliminary analy-

ses were designed to examine changes in the amount of lyso-

somes in the HaCaT cell line. Keratinocytes were treated with

proinflammatory cytokines [interleukin (IL)-1A, IL-17A,

IL-22, oncostatin M and tumour necrosis factor-a] to achieve

the ‘psoriasis-like’ phenotype, and then stained for the fluores-

cence microscope images. In the course of this work we con-

cluded that the number of lysosomes is reduced in stimulated

keratinocytes compared with controls (nonactivated cells). To

verify the validity of the obtained data, the expression of

genes responsible for lysosomal biogenesis (i.e. MiT family

genes: TFE3, TFEB, TFEC and MITF) by real-time quantitative

reverse-transcriptase polymerase chain reaction in patients’

skin biopsies was examined. The results showed downregula-

tion of TFE3, TFEB and MITF in both lesional and nonlesional

psoriatic skin compared with the normal skin from healthy

individuals. In turn, the level of the TFEC gene was elevated in

both cases, or unchanged in lesional vs. nonlesional tissue.

The above data indicate potential lysosome biogenesis distur-

bances, in the direction of lowering the efficiency of this pro-

cess in skin of patients with psoriasis. The obtained results

were compared with the activity of genes encoding calcineurin

subunits PPP3CA and PPP3CB. We observed reduced expres-

sion of both genes in psoriatic skin tissue, which may indicate

that dysfunction of factors in the MiT family can be aggra-

vated by impaired calcium homeostasis and their regulation

by calcineurin. These data may complement the lack of

knowledge about the role of lysosomes in the development of

inflammation of the skin and contribute to the development

of new therapeutic targets and strategies.

P024Secukinumab demonstrates significantly lowerimmunogenicity potential than ixekizumab inhuman in vitro assaysS. Spindeldreher,1 B. Maill�ere,2 E. Correia,2

M. Tenon,2 A. Karle,1 P. Jarvis1 and F. Kolbinger11Novartis Pharma AG, Basel, Switzerland and 2CEA-Saclay, Institute Frederic

Joliot, Gif sur Yvette, FranceSecukinumab, a fully human monoclonal antibody (mAb) that

selectively neutralizes interleukin-17A, has significant efficacy

in the treatment of moderate-to-severe plaque psoriasis and

psoriatic arthritis (PsA). It demonstrates a rapid onset of action

and sustained responses with a favourable safety profile and

< 1% immunogenicity in the phase III programme. Secuk-

inumab has previously demonstrated lower potential for

immunogenicity than other biotherapeutics used to treat psori-

asis and PsA in in vitro assays. Here we extended the analysis

and compared the T-cell precursor frequencies against 4 mAbs

(secukinumab, ixekizumab, adalimumab and ustekinumab).

Two sets of 16 healthy donors were analysed (study 1 and

study 2). Immunogenic potential was evaluated using an

in vitro T-cell-amplification assay to measure the frequency of

mAb-specific pre-existing T cells from these donors. Mono-

cyte-derived dendritic cells (DCs) were generated from

peripheral blood mononuclear cells and exposed in vitro to

mAbs or a positive control (keyhole limpet haemocyanin) and

matured. CD4 T cells were stimulated by matured protein-

loaded DCs and cultured for 21 days. An Elispot assay was

used to assess the antigen specificity of T-cell lines. The fre-

quency of pre-existing specific T cells was calculated from the

proportion of culture wells that reacted to the protein. The

data were analysed using a Wilcoxon rank test. In study 1,

one of 16 donors responded to secukinumab, generating one

T-cell line (mean frequency 0.02 cells per million T cells; low

immunogenicity potential). In contrast, nine of 16 donors

responded to ixekizumab (35 T-cell lines, frequency 0.54),

nine of 16 responded to adalimumab (15 T-cell lines, 0.21)

and six of 15 responded to UST (14 T-cell lines, 0.19), show-

ing moderate immunogenic potential. In study 2, one of 15

generated T-cell lines was specific for secukinumab, with a

mean frequency of 0.03 cells per million CD4 T cells (low

immunogenicity potential), while seven donors responded to

ixekizumab, with a frequency of 0.21–0.67 specific CD4 T





from gene to clinic

85ABSTRACTS

cells per million CD4 T cells (mean 0.16) (moderate immuno-

genicity potential). Secukinumab showed a low number of

donors responding with a low T-cell precursor frequency

compared with other mAbs and therefore has significantly

lower immunogenic potential. This is in line with observed

clinical immunogenicity rates. This investigation was spon-

sored by Novartis Pharma AG, Basel, Switzerland.

P025Decreased expression of interleukin-27 inmoderate-to-severe psoriasis and its anti-inflammatory role in an imiquimod-inducedpsoriasis-like mouse modelW. Chen,1 Y. Gong,1 X. Zhang,2 Y. Tong,1 X. Wang,3

C. Fei,1 H. Xu,1 Q. Yu,1 Y. Wang1 and Y. Shi11Shanghai Tenth People’s Hospital, Tongji University School of Medicine,

Shanghai, China; 2Second Military Medical University, Shanghai, China and3Huashan Hospital, Fudan University, Shanghai, ChinaPsoriasis is a T-cell-mediated chronic inflammatory skin dis-

ease characterized by aberrant keratinocyte hyperproliferation.

A recent study reported that interleukin (IL)-27, which plays

a versatile role in inflammatory skin disorders, could induce

the function of T helper (Th)1 cells in psoriasis. Further

studies found a suppression role of IL-27 to Th17. Here we

investigated and compared the expression of IL-27 and its

receptor in patients with moderate-to-severe psoriasis vs.

healthy controls. We further identified the role of IL-27 in

an imiquimod-induced psoriasis mouse model by injection

with IL-27 or IL-27p28 antagonist. The results showed that

the protein expression and distribution of IL-27 and its

receptor were decreased in the skin and peripheral blood of

patients with moderate-to-severe psoriasis compared with

healthy controls, and IL-27 concentration was significantly

decreased in patients with psoriasis. mRNA levels of

IL-27p28, WSX-1 and gp130 in patients with moderate-to-

severe psoriasis were significantly lower than those of

healthy controls; however, the expression level of EBI3

mRNA did not vary remarkably. Imiquimod-induced mice

treated with IL-27 showed a relatively mild clinical manifes-

tation. However, blocking the role of IL-27p28 in imiqui-

mod-induced mice significantly aggravated disease, and a

significant elevation of proinflammatory cytokines (inter-

feron-c and IL-17) was also observed. All these data sug-

gested that IL-27 may possibly act as an anti-inflammatory

cytokine in psoriasis. Our study also indicated the potential

function of IL-27 in psoriasis immunotherapy.

P026Secukinumab shows high and sustained efficacy inpatients with moderate-to-severe palmoplantarpsoriasis: 2.5-year results from the GESTURE studyA. Gottlieb,1 J. Sullivan,2 A. Kubanov,3 R. You,4

P. Regnault5 and J. Frueh51New York Medical College, New York, NY, U.S.A.; 2Holdsworth House

Medical Practice, Darlinghurst, Australia; 3State Scientific Center of

Dermatology, Venereology and Cosmetology, Moscow, Russian Federation;

4Novartis Institutes for BioMedical Research, Shanghai, China and 5Novartis

Pharma AG, Basel, SwitzerlandPalmoplantar psoriasis occurs in up to 40% of patients with

plaque psoriasis and is often resistant to treatment. It is associ-

ated with pain, functional limitations and greater impairment

of health-related quality of life compared with plaque psoriasis

on other parts of the body. Secukinumab, a fully human mon-

oclonal antibody that selectively neutralizes interleukin-17A,

has demonstrated significant efficacy in the treatment of mod-

erate-to-severe psoriasis and psoriatic arthritis, indicating rapid

onset of action, sustained responses and a favourable safety

profile. Here we report the long-term follow-up efficacy and

safety results from the GESTURE study, the first robust (2.5-

year) data reported in patients with moderate-to-severe pal-

moplantar psoriasis treated with secukinumab. GESTURE is a

double-blind, randomized, placebo-controlled, parallel-group,

multicentre phase IIIb study to investigate the safety and effi-

cacy of secukinumab 150 and 300 mg subcutaneous in 205

patients with moderate-to-severe palmoplantar psoriasis. As

previously reported, after 16 weeks of placebo-controlled

treatment, the primary end point, palmoplantar Investigator’s

Global Assessment (ppIGA) 0/1, and all secondary end points

of this study were met, demonstrating superiority of secuk-

inumab over placebo at week 16. An interim analysis at week

80 established the continuation of improvement of palmoplan-

tar disease for all efficacy parameters. The effect was sustained

through 2.5 years with 59.2% and 52.5% of patients in the

secukinumab 300-mg and 150-mg groups, respectively (mul-

tiple imputation) achieving clear or almost clear palms and

soles (ppIGA 0/1). Consistently with this observation, the

mean Palmoplantar Psoriasis Area and Severity Index percent-

age change from baseline reached �74.7% and �61.6% for

secukinumab 300 mg and 150 mg, respectively, at 2.5 years

(multiple imputation). The Dermatology Life Quality Index 0

or 1 response was achieved in 45.5% vs. 23.9% of patients in

the secukinumab 300-mg and 150-mg groups, respectively

[last observation carried forward (LOCF)]. Pain and function

of palms and soles were markedly improved with secuk-

inumab, as reflected by the Palmoplantar Quality of Life

Instrument overall scores, with 16.7% and 17.9% patients

experiencing no difficulty in hand and feet functionality in

secukinumab 300-mg and 150-mg groups, respectively

(LOCF). The safety profile was consistent with that seen in

secukinumab phase III trials. The most common adverse events

across all treatment arms were nasopharyngitis, upper respira-

tory tract infection and headache. GESTURE, the largest and

longest-duration randomized controlled trial to date, revealed

that secukinumab provides a novel treatment option for the

difficult-to-treat and infrequently studied palmoplantar psoria-

sis population by providing a strong and sustained response

through 2.5 years. This investigation was sponsored by Novar-

tis Pharma AG, Basel, Switzerland.



P027Efficacy and safety of infliximab in the treatment ofthe Chinese patients with psoriasisJ.-Z. Guo, W.-H. Wang and C.-L. ZhangPeking University Third Hospital, Beijing, ChinaTo analyse the clinical efficacy and safety in Chinese patients

with psoriasis treated with infliximab, all treated inpatients at

the Dermatology Department of Peking University Third

Hospital were reviewed. The types of psoriasis, Psoriasis Area

and Severity Index (PASI) score and clinical response were

analysed. Infliximab was given at a dose of 5 mg kg�1 by

intravenous infusion at weeks 0, 2 and 6, followed by mainte-

nance infusion every 8 weeks. From 2015 to 2017, 27 of 98

inpatients with psoriasis in our department were treated with

infliximab: 18 male, nine females, mean age

40.6 � 13.7 years (range 21–71). The mean duration of pso-

riasis was 17.6 � 9.9 years (range 0.4–40). Twenty-two cases

were of plaque psoriasis, including 14 male and eight female

patients. The mean baseline PASI was 19.0 � 11.4 (range

2.4–46.7). The mean plaque psoriasis baseline PASI was

17.8 � 10.7 (range 2.4–46.7). Most patients received three to

seven infusions. Fourteen patients, including 11 with plaque

psoriasis, strictly adhered to the therapeutic schedule before

14 weeks. In all 14 with least 14 weeks of strict adherence to

therapy, the average PASI score decreased from 18.7 to 2.7 at

the 14th week. The percentage change from baseline in PASI

reached 81% at the week 14. In 11 patients with plaque psori-

asis with at least 14 weeks of strict adherence to therapy, the

average PASI score decreased from 16.7 to 3.7 at the week 14.

The percentage change from baseline in PASI reached 81% at

the week 14 week. In total 37% of patients reached PASI 90

(≥ 90% improvement from baseline), 18% of patients reached

PASI 75 and 22% of patients reached PASI 50. One case aggra-

vated and one did not adhere to the therapeutic schedule

before 14 weeks. Two patients maintained PASI 90 for

10 months and 17 months, respectively. Five patients main-

tained PASI 75 and seven patients, including four with plaque

psoriasis, maintained PASI 50. One patient showed rebound

after 6 months without any treatment. Six cases relapsed,

including five with plaque psoriasis, where the improvement

in PASI score fell below 50% from baseline. None rebound in

3 months. Six of 27 (22%) patients had adverse reactions such

as aggravation, dizziness, shortness of breath, cold sweat,

blood pressure decrease, mild distending head pain, herpes

zoster, slight chest distress, shortness of breath and low-grade

fever. There were no severe adverse reactions. Infliximab has a

good clinical response and is relatively safe in the treatment of

the Chinese patients with psoriasis.

P028Secukinumab clinical outcomes in a tertiary referralcentreO. Jagun, S.T. Cheung, O. Jagun and S.T. CheungThe Royal Wolverhampton NHS Trust, Wolverhampton, U.K.Secukinumab is a fully human monoclonal antibody against

interleukin-17A. Long-term efficacy has been demonstrated in

clinical trials, with up to 76% of patients achieving ≥ 90%

improvement in Psoriasis Area and Severity Index (PASI 90) at

week 52 (Blauvelt A, Reich K, Tsai TF et al. Secukinumab is

superior to ustekinumab in clearing skin of subjects with

moderate-to-severe plaque psoriasis up to 1 year: results from

the CLEAR study. J Am Acad Dermatol 2016;76: 60–9). The

National Institute for Health and Care Excellence (NICE) rec-

ommends secukinumab in patients with severe psoriasis [PASI

and Dermatology Life Quality Index (DLQI) > 10] and in

those with contraindications, intolerance or failed responses to

other systemic therapies. The aim of this study was to evaluate

the appropriateness and efficacy of secukinumab in all the

patients treated in our tertiary referral centre. Patients were

identified from our pharmacy database and data were collected

from electronic patient records and research trial documenta-

tion between December 2013 and March 2017. The PASI and

DLQI scores were extracted at baseline and weeks 12 and

week 52. Sixteen patients were identified 88% (n = 14) of

whom met the criteria for severe psoriasis. Thirteen (81%)

had been on previous systemics, 13% (n = 2) had contraindi-

cations and 31% (n = 5) were intolerant to other systemics.

Seven were clinical trial patients, while nine were nontrial

patients; nine patients were biologic naive while seven had

previous biologics. An average PASI reduction of 80.6% was

observed after 12 weeks and 73.2% after 52 weeks. Of the

data available, 10% of patients achieved PASI 100, 40% PASI

90 and 30% PASI 75 at week 12, while 29% achieved PASI

100 and 43% PASI 75 at week 52. Overall, 90% (n = 10) and

80% (n = 6) of patients achieved the NICE criteria for

response assessment at weeks 12 and week 52, respectively, of

the data available. Our data demonstrate that secukinumab,

despite being more efficacious in biologic-naive patients, is

also effective in treatment-resistant patients who have failed

previous biologics at 1-year. More real-life data are required

to assess longer-term safety and efficacy.

P029Sustained response to adalimumab over multipleyears in patients with plaque psoriasis: analysesfrom the British Association of DermatologistsBiologic Interventions Register (BADBIR)B. Kirby,1 J.-F. Maa,2 T. Festini,2 B. Calimlim2 andO.R. Servın21St Vincent’s University Hospital, Dublin, Ireland and 2AbbVie Inc., North

Chicago, IL, U.S.A.Psoriasis is a life-long chronic disease requiring enduring

treatment. The introduction of biological therapy has greatly

improved psoriasis management, and data on real-world bio-

logics vs. conventional therapy are needed to understand ther-

apy profiles over time. BADBIR, a long-term

pharmacovigilance register, monitors the safety of biologics

and conventional therapy in patients with psoriasis in the U.K.

and Republic of Ireland. The tumour necrosis factor-a inhibi-

tor adalimumab is an approved treatment for moderate-to-

severe plaque psoriasis. Using BADBIR registry data, we

assessed response to adalimumab vs. conventional therapy





from gene to clinic

87ABSTRACTS

every 6 months through year 3 and then yearly (observed data

through September 2016) in patients with plaque psoriasis.

Patients initiated or switched to a biologic or conventional

therapy within 6 months of registration; patients initiating

conventional therapy had to have Psoriasis Area and Severity

Index (PASI) ≥ 10 and Dermatology Life Quality Index (DLQI)

>10 (no PASI/DLQI requirement for biologics). PASI, Physi-

cian’s Global Assessment (PGA) and DLQI were assessed. In

total 3311 patients treated with adalimumab (baseline mean

age 45 years; 60% men; mean � SD PASI 12.4 � 8.7; mean

DLQI 13.2 � 9.0; mean PGA 3.4 � 1.5) and 4382 treated

with conventional therapy (baseline mean age 44 years; 56%

men; mean PASI 14.9 � 8.1; mean DLQI 15.4 � 6.9; mean

PGA 3.8 � 1.0) were included. Over 6 years, the proportions

of patients with PASI 75, 90 and 100 responses were

significantly greater with adalimumab than with conventional

therapy, with response rates maintained at 71.8–77.5% vs.

37.2–52.2%, P < 0.001; 50.1–53.6% vs. 17.4–31.9%,P < 0.01 and 30.1–33.3% vs. 7.5–15.9%, P < 0.01, respec-

tively. The proportions of patients with PGA 0–1 over 6 years

were also significantly higher in patients treated with

adalimumab vs. conventional therapy, with response rates

maintained at 65.9–71.6% vs. 29.6–40.8%, P < 0.001. Simi-

larly, the proportions of patients with DLQI 0–1 were greater

with adalimumab vs. conventional therapy through year 4

(60.3–67.4% vs. 23.8–31.5%); only 20 patients had DLQI

data beyond year 4. These results demonstrate that adali-

mumab significantly improved the signs and symptoms of pla-

que psoriasis compared with conventional therapy. Moreover,

the clinical and quality-of-life responses to adalimumab in

patients with plaque psoriasis were sustained over multiple

years in this real-world experience.

P030Successful treatment of psoriasis withsecukinumab after ustekinumab in a patient withmultiple sclerosisS. Kaneko,1 H. Oguro2 and E. Morita11Department of Dermatology and 2Department of Neurology, Shimane

University Faculty of Medicine, Izumo, JapanA 49-year-old man had been treated with steroid and vitamin

D3 ointment for psoriasis vulgaris since 25 years of age. He

was diagnosed with multiple sclerosis at 42 years of age. Prior

to treatment, his Psoriasis Area and Severity Index (PASI) was

16.9, and his Expanded Disability Status Scale (EDSS) score

was 2. Psoriasis eruption were cleared after using the steroid

pulse therapy induction to treat multiple sclerosis. After that

treatment, he developed hypertension and diabetes. When

interferon-b was administered as maintenance therapy for

multiple sclerosis, joint pain and psoriatic skin eruptions

occurred. When the patient was 43 years old, therapy with

ustekinumab was introduced, as the other immunosuppressive

therapies were unsuccessful. Although the skin eruptions were

relieved, the joint pain worsened in both hands and feet, and

deterioration was confirmed on X-ray. At 47 years of age, his

EDSS score was 7.5, at which time his therapy was switched

to secukinumab. His psoriatic eruptions were relieved, PASI

became clear, and joint pain was reduced. His C-reactive pro-

tein level, which was initially high, had also decreased.

Although multiple sclerosis is a progressive demyelinating dis-

ease, the EDSS score of 7.5 in our patient did not adversely

deteriorate after the administration of secukinumab. According

to the Group for Research and Assessment of Psoriasis and

Psoriatic Arthritis (GRAPPA) recommendations, the most com-

monly recommended biologics for the treatment of psoriatic

arthritis are the tumour necrosis factor (TNF) inhibitors inflix-

imab and adalimumab. As TNF inhibitors are contraindicated

in patients with multiple sclerosis, ustekinumab was the only

biologic available for this patient before the recent approval of

secukinumab, an interleukin-17A inhibitor. This case demon-

strates the successful administration of ustekinumab, and

secukinumab may have shown effects not only on psoriasis

but also on multiple sclerosis.

P031Development of pulmonary sarcoidosis in a patientwith psoriasis under treatment with ustekinumab:comorbidity or drug-related ‘paradoxical’phenomenon?C. Fotiadou, E. Lazaridou, E. Sotiriou andD. IoannidesFirst Department of Dermatology, Aristotle University Medical School,

Thessaloniki, GreecePsoriasis is a chronic, inflammatory skin disorder with a com-

plex pathophysiology. Psoriasis pathogenesis is mediated by

the activation of both T helper (Th)1 and Th17 lymphocytes.

Sarcoidosis is a granulomatous disease that is also characterized

by Th1/Th17-driven inflammation. Some authors believe that

psoriasis pathogenesis is, in some cases, associated with that

of sarcoidosis, while others have described the paradoxical

induction of certain autoimmune conditions such as sarcoido-

sis after the initiation of psoriasis treatment with antitumour

necrosis factor (anti-TNF)-a biological agents. Here we

describe the case of a 32-year-old man with a 5-year history

of mild psoriasis. During the last year his condition had dete-

riorated (Psoriasis Area and Severity Index 15.2, Dermatology

Life Quality Index 12) and he was treated with ciclosporin

150 mg twice daily. After 6 months with no adequate

response, it was decided to change treatment to ustekinumab

45 mg, an anti-interleukin (IL)-12/23 monoclonal antibody

with an approved dosing regimen for psoriasis. After the first

two injections (0 and 4 weeks) his psoriasis ameliorated

reaching PASI 75, but he presented a thoracic pain and mild

fever (37.2 °C). Chest X-ray and computed tomography

showed bilateral hilar lymphadenopathy with disseminated

nodules in the lungs. Sputum culture and Mantoux test were

negative for Mycobacterium tuberculosis. Bronchoscopy, along with

the histological examination of a representative lesion, con-

firmed the diagnosis of sarcoidosis. The patient stopped ustek-

inumab and started treatment with systemic steroids. This is

one of the very few cases in the literature describing the

development of sarcoidosis after the initiation of psoriasis



treatment with ustekinumab. Ustekinumab itself was given,

off-label, for the treatment of sarcoidosis. More research and

more experience is needed in order to certify whether sar-

coidosis is a comorbidity of psoriasis or whether ustekinumab

may, in some cases, induce autoimmune diseases such as

sarcoidosis.

P032Factors associated with the choice of the firstbiologic in psoriasis: real-life analysis from thePsobioteq cohortE. Sbidian,1 C. Giboin,2 H. Bachelez,3 C. Paul,4

M. Beylot-Barry,5 A. Dupuy,6 M. Viguier,7 J.-P. Lacour,8 J.-L. Schmutz,9 P. Bravard,10 E. Mah�e,11

N. Beneton,12 L. Misery,13 E. Delaporte,14

P. Modiano,15 S. Barbarot,16 S. R�egnier,17

D. Jullien,18 M.-A. Richard,19 P. Joly,20 F. Tubach2 andO. Chosidow1

1Hopitaux Universitaires Henri Mondor, Cr�eteil, France; 2Hopitaux

Universitaires Piti�e Salpetri�ere, Charles Foix, Paris, France; 3Hopital Saint-

Louis, Paris, France; 4Hopitaux Universitaires de Toulouse, Toulouse, France;5Hopital Saint-Andr�e, Bordeaux, France; 6Centre Hospitalier Universitaire de

Rennes, Rennes, France; 7Hopitaux Universitaires Robert Debr�e, Reims,

France; 8Centre Hospitalier Universitaire de Nice, Nice, France; 9Centre

Hospitalier R�egional Universitaire de Nancy, Nancy, France; 10Groupe

Hospitalier du Havre, Le Havre, France; 11Hopital Victor Dupouy, Argentueil,

France; 12Centre Hospitalier du Mans, Le Mans, France; 13Centre Hospitalier

R�egional Universitaire de Brest, Brest, France; 14Centre Hospitalier R�egional

Universitaire de Lille, Lille, France; 15Groupement des Hopitaux de l’Institut

Catholique de Lille, Lille, France; 16Centre Hospitalier Universitaire de

Nantes, Nantes, France; 17Hopitaux Universitaires Cochin, Paris, France;18Hopital Edouard Herriot, Lyon, France; 19Hopital La Timone, Marseille,

France and 20Rouen University Hospital, Rouen, FranceDecision making is a complex process. The aim of our study

was to assess factors associated with the choice of the first bio-

logical treatment in patients with moderate-to-severe psoriasis.

Data on all patients included in the French prospective, obser-

vational, cohort, Psobioteq, and initiating a first biological

prescription between July 2012 and July 2016 were analysed.

Demographic information and clinical features were collected

during routine clinical assessments by the dermatology team

at the recruiting centres using a standardized case report form.

The primary outcome was the nature of the first biological

treatment. Four groups were identified: adalimumab, etaner-

cept, ustekinumab and infliximab. Factors associated with the

choice of the first biological agent were determined by a

multinomial logistic regression model adjusted on year of

inclusion. The study population included the 830 biologic-

naive patients who initiated a first biological agent. The mean

age was 46.6 � 13.9 years, and 318 patients (38.3%) were

female. The most commonly prescribed biologic was adali-

mumab: 355 (42.8%) patients, then etanercept (n = 247,

29.8%), ustekinumab (n = 194, 23.4%) and infliximab

(n = 34, 4.0%). In the multinomial logistic regression analy-

sis, patients were significantly more likely to receive adali-

mumab if they had severe psoriasis or if they had psoriatic

arthritis compared with etanercept [adjusted odds ratio (aOR)

0.42, 95% confidence interval (CI) 0.16–1.07] and ustek-

inumab (aOR 0.15, 95% CI 0.04–0.52). Patients were signifi-

cantly more likely to receive ustekinumab (aOR 2.39, 95% CI

1.04–5.50) if they had a positive screening for latent tubercu-

losis compared with adalimumab. Younger patients were also

more likely to receive ustekinumab. Patients with chronic

obstructive pulmonary disease were more likely to be pre-

scribed ustekinumab or etanercept compared with adali-

mumab. There was a trend in favour of etanercept

prescription in patients with cardiovascular comorbidities and

metabolic syndrome and in patients with a history of cancer.

In conclusion, we identified patient- and disease-related fac-

tors that have important influence on the choice of the first

biological agent in clinical practice. Clinicians appear to have a

holistic approach to patient characteristics when choosing a

biological agent in psoriasis.

P033The Psoriasis Association as a role model for othersupport groups: how far can (dare) we go?H.H. OonNational Skin Centre, Singapore, SingaporePsoriasis is visible skin disorder with significant psychosocial

impact and burden. The Psoriasis Association is a dermatology

support group formed in 1982. It is run by volunteers com-

prised of patients, relatives, nurses, allied health professionals,

social workers and doctors. Successful activities include the

annual World Psoriasis Day, media campaigns, conventional

talks by doctors, psychologists, group therapy and screening

for comorbidities. Less conservative but equally successful

activities include exercise sessions, art therapy, healthy cook-

ing at a gourmet kitchen, children’s games and creation of

music videos. In 2011, the Eczema Support Group was started,

tapping on the successful model of the Psoriasis Association

with its large patient following, dynamism and strong out-

reach. Acne Awareness Day was a day-long event in 2016

with activities devoted to teen and adult patients with acne

and their caregivers. Interactive games and multidisciplinary

talks incorporating pharmacists and a psychologist were con-

ducted. Key events included a low glycaemic load lunch to

underscore the importance of diet and acne, and a video high-

lighting awareness on acne and the importance of early treat-

ment. Support groups offer a unique experience and fill the

gaps of the traditional model of care of the dermatologist

clinic by viewing skin diseases in a holistic manner where

patient, family, school, workplace and society are closely

intertwined. The successful model of one support group can

propel the development of other support groups in both a lin-

ear and synergistic manner that addresses the whole person

with proven techniques and ideas.





from gene to clinic

89ABSTRACTS

P034Paradoxical psoriasis caused by tumour necrosisfactor inhibitor therapy: a model system to studythe interplay between environmental triggers andgenetic susceptibility?T. Maruthappu,1 A. Connolly,1 S. Mahil,1,2

B. Kirkham,3 P. DiMeglio2 and C. Smith1,21St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Trust,

London, U.K.; 2King’s College London, London, U.K. and 3Department of

Rheumatology, Guy’s and St Thomas’ NHS Trust, London, U.K.Paradoxical psoriasis (PXP) is an uncommon complication of

treatment with tumour necrosis factor inhibitor (TNFi) thera-

pies and can pose a diagnostic and therapeutic challenge. It

occurs in 2.3–5% of patients receiving TNFi therapy irrespec-

tively of the underlying indication and can require cessation

of therapy. To date, the mechanism underlying the develop-

ment of PXP has remained elusive. We report seven patients

(four female, three male, aged 34–43 years) who developed

PXP following treatment with TNFi therapy: adalimumab

(n = 3), infliximab (n = 2) and certolizumab (n = 2). TNFis

were prescribed for a variety of inflammatory conditions:

ankylosing spondylitis (one positive HLA-B27) (n = 2), psori-

atic arthritis with mild scalp psoriasis (n = 2), plaque psoriasis

(n = 1), neurosarcoidosis (n = 1) and inflammatory bowel

disease (n = 1). Six of the seven patients were biologic na€ıve

prior to the initiation of the TNFi. Four of the patients devel-

oped paradoxical palmoplantar pustular psoriasis affecting both

the palms and soles. Of these, one patient developed markedly

hyperkeratotic scalp psoriasis associated with extensive hair

loss. Two patients developed de novo plaque psoriasis of moder-

ate severity, with thin inflammatory plaques predominantly

affecting the and trunk and limbs. Consistently with previously

reported literature, the mean time to onset of PXP was

17 months. Topical therapies had limited efficacy in six of the

seven patients and subsequently the causative TNFi was

stopped. Three were switched to an alternative TNFi, resulting

in the resolution of PXP in one patient and partial improve-

ment in another. Two patients were commenced on ustek-

inumab and gradually improved. The mean time to resolution

was 14 months; however, five of the seven patients have per-

sistent, albeit improving disease. The pathogenic mechanisms

underpinning PXP have remained elusive so far, but a disrup-

tion in cytokine balance mediated by TNF blockade, with dys-

regulated type I interferon signalling, has been reported. No

predisposing factors for PXP, other than the use of TNFis, has

been identified to date, although a genetic component is

widely suspected. Thus, PXP represents an ideal model system

for a proof-of-principle study unravelling the complex mecha-

nistic interplay between a specific environmental trigger, that

is TNFi, genetic susceptibility and immune dysregulation,

namely aberrant type I interferon response. Due to the infre-

quency of the condition, we welcome a multicentre effort to

recruit carefully phenotyped patients with PXP for future

genetic and functional studies.

P035The coexistence of generalized pustular psoriasisand pemphigus foliaceus in a woman with Cushingsyndrome: a case reportA. Kusumawardani,1,2 S.E. Ilona,1,2 D.A. Mira3,4 andSuradi Radiono3,4

1Sebelas Maret University, Surakarta, Indonesia; 2Moewardi Hospital,

Surakarta, Indonesia; 3Gajah Mada University, Yogyakarta, Indonesia and4Sardjito Hospital, Yogyakarta, IndonesiaPsoriasis is a chronic skin disease, which can be associated

with other skin and systemic disease. Bullous skin disease is

one of the skin diseases associated with psoriasis. Coexistence

of generalized pustular psoriasis (GPP) and pemphigus foli-

aceus (PF) is very rare. The contrasting treatment of GPP and

PF in a patient with Cushing syndrome was a major challenge

in this case. A 33-year-old woman complained of new lesions

of erythematous plaques appearing with fever over the previ-

ous 10 days and multiple flaccid bullae. The patient had had

GPP for 1 year and since then she has received methyl pred-

nisolone (MP) and methotrexate. There was no history of sim-

ilar illness in her family. Physical examination demonstrate

signs of Cushing syndrome. Dermatological examination

revealed multiple erythematous plaques, vesicles, pustules and

erosions in an annular shape with scale accompanied by mul-

tiple striae on the anterior and posterior trunk and abdomen.

On the upper extremities, posterior trunk and gluteus were

vesicles and flaccid bullae on erythematous skin. There was no

mucosal involvement or nail abnormalities. Histopathological

examinations using haematoxylin and eosin staining taken

from two different places were both consistent GPP and PF.

Examination of direct immunofluorescence supported PF. The

patient is being treated with MP and ciclosporin. In the first

2 months of therapy the patient relapsed several times during

the tapering off MP. This patient was maintained with an MP

dose of 8 mg per day and ciclosporin 125 mg per day, and

their condition has been controlled for 9 months. GPP and PF

are two very different skin diseases, both clinically and patho-

genetically. Their coexistent clinical expression possibly

happened because of T-cell-dependent chronic immunostimu-

lation and phototherapy. In PF and pemphigus vulgaris, their

specific human leucocyte antigen allele, namely HLA-DRB1,

has been identified, which is also a specific gene in psoriasis.

Systemic corticosteroids are the mainstay of therapy for PF,

but not in the routine management of psoriasis, especially for

PPG. Currently there are no therapy guideline for their coexis-

tence, therefore a strategy for management of corticosteroid

administration is needed.

P036Retrospective audit on psoriasis, assessment andmanagement: National Institute for Health andCare Excellence guideline CG153 within adermatology departmentM. Verma, A. Leong and S. VelangiQueen Elizabeth Hospital Birmingham, Birmingham, U.K.



A retrospective clinical audit was conducted to evaluate the

assessment and management of patients with psoriasis within

a tertiary centre. The data were compared against the U.K.

National Institute for Health and Care Excellence (NICE) ‘Pso-

riasis: assessment and management’ (CG153). The parameters

reviewed included use of validated tools: Psoriasis Area and

Severity Index (PASI), Patient’s Global Assessment, Dermatol-

ogy Life Quality Index (DLQI) and PEST (Psoriasis Epidemio-

logical Screening Tool). The aims were to assess current

clinical practice as measured against the NICE standards with

review of services including rheumatology referral, ultraviolet

(UV)B phototherapy and use of systemic nonbiological treat-

ments. UVA phototherapy and systemic biological treatments

were not assessed. Data were collected from 50 patients via

random selection using data informatics. One patient was

excluded (no psoriasis). A hospital electronic database was

used to collate patient data, which were entered into a Micro-

soft Excel spreadsheet using the Clinical Audit Toolkit (NICE

CG153) for generation of results. Use of Patient’s Global

Assessment had a compliance of 0%. Use of UVB photother-

apy had 53% compliance and nonbiological therapies 62%

compliance. PEST (annual psoriatic arthritis assessment) had

14% compliance. Rheumatology referral and offers of second-

line therapies when phototherapy failed had 100% compli-

ance. PASI and DLQI assessment completion were both 82%,

and Physician’s Global Assessment compliance was 55%. PASI

is currently the most utilized and validated clinical tool to

assess severity in patients with psoriasis. Documentation of

body surface area compliance was 87%, with difficult-to-treat

sites at 64% and recording of systemic upset at 60%. Studies

have shown that use of both PASI and Patient’s Global Assess-

ment simultaneously is redundant. Result analysis and inter-

pretation were processed automatically by the national toolkit

database; however, raw data interpretation led to plausible

rationale for some discrepancies. To increase PASI, PEST and

DLQI compliance with the NICE guidance, we have designed

and implemented a mandatory electronic pro forma that eases

data collection and provides prompts for essential information

for completion within consultations. Outcomes for the project

include a ‘how to assess patients with psoriasis’ template for

consultations, departmental audit presentation and reaudit

after 1 year alongside the NICE update. The British Association

of Dermatologists recommends a central resource for scoring

tools and disease-specific pro formas to assess patients, but

currently there are none. Clinicians will use standard scoring

systems that will allow appropriate classification of patients

and individualized treatment plans. These are crucial in the

management of patients with psoriasis.

P037Role of Thevetia neriifolia in the treatment ofpsoriasis: clinical case reportD. Maryam,1 S. Souad,2 O.S. Charifa3 andS.-B. Rachida1,31Center Anti Poison and Pharmacovigilance of Morocco and 3Faculty of

Medicine and Pharmacy, Mohammed V University, Rabat, Morocco and

2Botanical, Mycology and Environmental Laboratory, Ibn Tofail University,

Kenitra, MoroccoMany pharmaceutical companies have become very interested

in investigating the therapeutic activities of Thevetia neriifolia in

the treatment of various disorders in humans, especially psori-

asis. Thevetia neriifolia belongs to the family Apocynaceae and is

commonly called oleander yellow or lucky nut tree. Thevetia

neriifolia contains a milky sap that can be extracted from either

leaves or seeds. This sap is full of active substances and has

antioxidant and anti-inflammatory properties. In addition, it

may prevent the cell damage caused by psoriasis. We describe

the case of male patient, 31 years old, who lost his parents

and was very affected by their death. Firstly, he developed

erythrodermic psoriasis lesions (psoriasis drops) in the inner

side of both feet. The plaque psoriasis went on to cover most

of the body without fever. His emotional stress was implicated

in the induction of the psoriasis. He has been using topical

steroids since July 2016, with no improvement of the condi-

tion (Arena C, Morin AS, Blanchon T et al. Impact of glucocor-

ticoid-induced adverse events on adherence in patients

receiving long-term systemic glucocorticoid therapy. Br J Der-

matol 2010; 163: 832–7). The patient used the milky sap of

T. neriifolia for 1 month. During this period we noticed a

favourable evolution of his disease. The erythrodermic psoria-

sis lesions started to disappear gradually after 2 weeks of daily

application of T. neriifolia on his skin. The patient is still under

treatment. Through this clinical case report, T. neriifolia can be

considered a potential source in the manufacture of drugs

against psoriasis.

P038Large-scale imputation of killer cellimmunoglobulin-like receptor copy number inpsoriatic arthritisR. Ahn,1 D. Vukcevic,2,3 A. Motyer,2.3 D. Ellinghaus,4

L.C. Tsoi,5 R.P. Nair,5 C. Palmer,6 J. Oksenberg,1

J. Foerster,6 J.T. Elder,5 A. Franke,4 S. Leslie2,3 andW. Liao1

1University of California San Francisco, San Francisco, CA, U.S.A.;2University of Melbourne, Parkville, Australia; 3Murdoch Children’s Research

Institute, Parkville, Australia; 4Kiel University, Kiel, Germany; 5University of

Michigan, Ann Arbor, MI, U.S.A. and 6University of Dundee, Dundee, U.K.Killer cell immunoglobulin-like receptors (KIRs) are known to

regulate innate immune responses via interaction with human

leucocyte antigen (HLA) molecules. KIR genes, including

KIR2DS1 and KIR2DS2, have previously been implicated in pso-

riatic arthritis susceptibility. However, these previous studies

had limited power to detect associations due to their limited

sample size To overcome the expense of directly genotyping

KIR genes, we implemented the KIR*IMP method to impute

KIR copy number from single-nucleotide polymorphisms on

chromosome 19 from a cohort from the University of Califor-

nia San Francisco (UCSF, n = 864) and the PAGE consortium

(n = 9482). Samples had previously been genotyped on either

the Affymetrix Axiom U.K. Biobank chip (UCSF) or the





from gene to clinic

91ABSTRACTS

Illumina Immunochip (PAGE consortium). Multivariate logistic

regression that accounted for patient ancestry (as revealed by

principal components analysis) and known high-risk HLA

genotypes revealed that KIR2DS4 deletion copy number was

significantly associated with psoriatic arthritis (P = 0.02). We

also found evidence for interaction between KIR2DS4 deletion

copy number and HLA-C1 (P = 0.01). Our study suggests that

future large-scale studies of typed and imputed KIR (both

copy number and alleles) in psoriatic arthritis are warranted

to discover and confirm novel KIR associations.

P039Psoriasis following PD-1 inhibitor therapy: featuresand treatmentP. O’Connor and J.P. DutzUniversity of British Columbia, Vancouver, BC, CanadaPatients with stage IV melanoma have a 1-year survival rate

< 25%. Advances in therapies that harness antitumour immu-

nity by inhibiting immune checkpoints such as programmed

cell death (PD)-1 have revolutionized the treatment of meta-

static melanoma. The cutaneous toxicities of these drugs can

cause substantial morbidity resulting in cessation of treatment.

The safest and most effective treatments for the cutaneous

side-effects of immune checkpoint inhibitors are not known.

Our aim was to review clinician experience and published

data on the features and management of psoriasis in patients

on PD-1 inhibitor therapy. We performed a case review and

structured literature review. We present three cases of palmo-

plantar and small plaque psoriasis occurring during treatment

with the PD-1 inhibitor pembrolizumab for metastatic mela-

noma. In one case the patient responded to pembrolizumab

but failed topical treatment of psoriasis, resulting in temporary

discontinuation of the immunotherapy. Successful treatment

with methotrexate allowed reintroduction of pembrolizumab.

The patient subsequently had progression of her metastatic

disease. Review of published literature revealed that PD-1 inhi-

bitor-related psoriasis can present with multiple morphologies,

with an increased frequency of the palmoplantar pustulosis

and small plaque types. In patients with pre-existing plaque-

type psoriasis a transition to small plaque morphology after

PD-1 inhibition is common. The most frequently reported

treatments are topical corticosteroids and acitretin, with varied

outcomes. Systemic immunosuppressants including methotrex-

ate and tumour necrosis factor-a inhibitors have been used to

treat other PD-1 inhibitor toxicities (colitis, arthritis); we pro-

pose these treatments may be an option for PD-1 inhibitor-

induced psoriasis.

P040Evaluation of body composition in patients withpsoriasis treated with ustekinumabM. Galluzzo,1 S. D’Adamio,1 R. Pastorino,2 L. Bianchi1

and M. Talamonti11Department of Dermatology, University of Rome ‘Tor Vergata’, Rome, Italy

and 2Section of Hygiene, Institute of Public Health, Catholic University of

the Sacred Heart, Rome, Italy

There is evidence that patients with psoriasis have increased

visceral adiposity, which represents not only an energetic

deposit but also an endocrine organ secreting adipocytokines.

The main goal of psoriatic therapies is to control the disease

and its clinical manifestations. The use of biological drugs,

such as antitumour necrosis factor (anti-TNF)-a agents, seems

to associate with an increase in adiposity. In the literature it is

reported that ustekinumab does not increase body mass index

(BMI) in patients with chronic plaque psoriasis, but there are

no studies on changes of the body composition in these

patients. Unfortunately, BMI fails to distinguish body compo-

nents such as fat mass and free fat mass in single individuals.

On the other hand, obesity may influence the therapeutic

approach to psoriasis and the clinical response to treatment. In

fact, adipose tissue may alter the volume of distribution, limit-

ing the efficacy of the drugs. The purpose of this study was to

investigate the body composition in patients with psoriasis

treated with ustekinumab using bioelectrical impedance analy-

sis and to correlate the bioelectrical impedance data with clini-

cal response to treatment. The study population consisted of

73 patients affected by moderate-to-severe chronic plaque pso-

riasis, naive to biological treatment and treated with ustek-

inumab for at least 1 year. All anthropometric measurements,

including weight, height and waist circumference, were col-

lected at baseline, after 6 months of treatment and then after

1 year. For each patient, we evaluated body composition

using bioelectrical impedance analysis and BiaVector analysis.

Linear mixed-effect models for repeated measures were

applied in order to assess the differences in the body composi-

tion from baseline to 6 and 12 months. For each variable of

the body composition, we fit a linear mixed-effect models

where time (baseline, 6 months and 12 months) and con-

founding factors were the explanatory variables. Significant

decrease were found at month 6 for weight (�0.88 kg, P=

0.03), BMI (�0.30 kg m�2, P= 0.03) and fat mass (�1.06,

P= 0.03). Contextually, free fat mass and total body water

showed increases of 1.06 (P= 0.03) and 0.78 (P= 0.02),

respectively. The significant changes from baseline were not

confirmed at month 12. A significant increase was found at

month 12 for body cell mass (2.63, P < 0.001) and phase

angle (0.60, P < 0.001) In addition, a significant increase was

found for intracellular water (2.42, P < 0.001), and a signifi-

cant decrease for extracellular water (�2.37, P < 0.001).

Lastly, considering the response to treatment, we did not find

a difference between the rate of responders and the body

composition. This is the first study to analyse body composi-

tion changes in patients treated with ustekinumab, and in con-

trast with data reported in studies on anti-TNF-a drugs, we

can say that ustekinumab does not increase adipose tissue, and

it appears to improve intracellular hydration. In addition, the

efficacy of the drug does not appear to be correlated with the

patient’s body composition.



P041Characteristics and risk profile of patients withpsoriasis included in the Turkish national registryPSR-TRN. Onsun,1 E.B. Baskan,2 D. Dizman,1 D.B. Ozkaya,3

A.C. Erkılıc,4 G. Ozarmagan5 and M.A. Gurer6

1Bezmi Alem University, Istanbul, Turkey; 2Uludag University, Bursa,

Turkey; 3Bezmi Alem University, Bursa, Turkey; 4Yeditepe University,_Istanbul, Turkey; 5Istanbul University, Istanbul, Turkey and 6Gazi

University, Ankara, TurkeyThe aim of this study was to assess the characteristics and associ-

ated comorbidities of patients with psoriasis in Turkey in a real-

life setting. The psoriatic arthritis registry of Turkey (PSR-TR) is

the only multicentre web-based registry for psoriasis, and was

established in 2006. Detailed data between 2006 and 2017 for

demographics of psoriasis, treatment profiles and comorbidities

were retrieved from PSR-TR web-based records. The median

age of the 8976 patients in the registry was 38.8 years [in-

terquartile range (IQR) 27.3–51.9]; 4492 (50.0%) were female,

6027 (67.1%) were married and 1777 (19.8%) had a university

degree at the time of the first visit. The median body mass index

was 26.8 kg m�2 (IQR 23.2–30.8). Of the 8976 patients in the

registry, 1321 (14.7%) had at least one concomitant disease at

the time of the first visit. The three most commonly reported

concomitant diseases were hypertension (710, 7.9%), diabetes

mellitus (430, 4.8%) and hypercholesterolemia (246, 2.7%).

Of the patients in the registry; 2527 (28–2%) had mild psoriasis

based on Psoriasis Area and Severity Index (PASI) and 1006

(11.2%) had a PASI score ≥ 10. At the first visit, 4536 (50.5%)

had used at least one type treatment and 4440 (49.5%) patients

did not use any type of treatment, or no details were recorded

in the database. During the follow-up visit, if a patient had used

any treatment at any of the follow-up visits, it was accepted as

treatment used during follow-up. During follow-up visits, 3613

(40.3%) used at least one type of treatment, while 5363

(59.7%) patients did not used any type of treatment or no

details were recorded in the database. Overall 4557 (50.8%)

used topical treatment at the first visit and/or any of the follow-

up visits, 824 (9.2%) received phototherapy at the first visit

and/or any of the follow-up visits, and 3343 (37.2%) used at

least one systemic treatment at the first visit and/or any of the

follow-up visits. The most commonly used systemic treatment

was methotrexate (2212, 24.6%). In total 1169 (13.0%) used at

least one biological treatment at the first visit and/or any of the

follow-up visits. Our results showed a similar prevalence of

demographic features and comorbidities to those of patients

with psoriasis.

P042Treatment profile of patients with moderate-to-severe psoriasis included in the Turkish nationalregistry PSR-TRN. Onsun,1 E.B. Baskan,2 D. Dizman,3 D.B. Ozkaya,1

A.C. Erkılıc,4 G. Ozarmagan5 and M.A. G€urer61Bezmi Alem University, Istanbul, Turkey; 2Uludag University, Bursa,

Turkey; 3Bezmi Alem University, Istanbul, Turkey; 4Yeditepe University,

Istanbul, Turkey; 5Istanbul University, Istanbul, Turkey and 6Gazi

University, Ankara, TurkeyThe aim of this study was to assess the treatment profile of

patients with moderate-to-severe psoriasis in Turkey in a real-

life setting. The psoriatic arthritis registry of Turkey (PSR-TR)

is the only multicentre web-based registry for psoriasis,

and was established in 2006. Detailed data between 2006 and

2017 for demographics of psoriasis, treatment profiles and

dermatologist preferences were retrieved from PSR-TR web-

based records. Of the 8976 patients in the registry, 1006

(11.2%) had a Psoriasis Area and Severity Index ≥ 10. At the

first visit, 640 (63.6%) of the patients had received any type

of treatment; however, topical therapy was the preferred ther-

apy in 338 (33.6%) of the patients and all had received topi-

cal therapy at some time during the follow-up. In total 272

(27%) of the patients received at least one systemic treatment

at the first visit, and the rate increased to 55.4% at the follow-

ing visits. Methotrexate was the most common preferred

systemic agent, used in 138 (13.7%), followed by acitretin in

97 (9.6%). Phototherapy was the preferred treatment in 147

(14.6%). At least one biological treatment was prescribed in

116 (11.5%) at the first visit, which increased to 351

(34.9%) at the following visits. Infliximab was the most pre-

scribed biologic, in 42 (4.2%). Our results demonstrate that a

substantial percentage of patients still do not receive the treat-

ment they deserve, and topical therapy is the first choice at

the initial and follow-up visits.

P043An ongoing independent study to monitor theuptake of interleukin-17 inhibitors among U.S.dermatologistsJ. Robinson and L. PriceSpherix Global Insights, Exton, PA, U.S.A.Each quarter, an online survey of approximately 100 derma-

tologists in clinical practice is fielded by an independent mar-

ket research firm, which specializes in tracking biological

uptake in various autoimmune conditions including psoriasis

and psoriatic arthritis. The most recent survey, fielded in May

2017, finds that since the introduction of ixekizumab the per-

centage of biologic-treated patients with psoriasis on an inter-

leukin (IL)-17 inhibitor has doubled, and they currently

account for nearly one in five biologic-treated patients. Despite

the potential for IL-17 class cannibalization, the growth of

ixekizumab and secukinumab over the past year has been pri-

marily at the expense of the established tumour necrosis factor

inhibitors, adalimumab and etanercept. A third IL-17 inhibi-

tor, brodalumab, was approved by the U.S. Food and Drug

Administration (FDA) in February 2017; however, uptake of

this new agent is negligible. One-third of the surveyed derma-

tologists (n = 103) have no intention of ever using bro-

dalumab, primarily due to the product’s associated suicide

risk, black box warning and required risk evaluation and miti-

gation strategies programme. In a head-to-head comparison of

ixekizumab and secukinumab, dermatologists largely view the

two agents as interchangeable. However, among those who





from gene to clinic

93ABSTRACTS

perceive a difference between the two agents, 78% believe

ixekizumab is superior when asked to compare the two for

‘efficacy in skin clearance’. Twice as many dermatologists also

believe that ixekizumab possesses a faster onset of action, an

attribute important to patients. Secukinumab does hold a per-

ceived advantage over ixekizumab for effectiveness in psoriatic

arthritis, where it is currently the only FDA-approved IL-17

agent available. Future expectations for the IL-17 class are

favourable, with half of the surveyed dermatologists anticipat-

ing an increase in their use of both ixekizumab and secuk-

inumab in the second half of 2017. To what extent the IL-17

inhibitors can grow will be dependent on two leading factors:

competition from recently approved guselkumab, which will

compete for a similar patient type, and restrictions by man-

aged care, which dermatologists note are the greatest barriers

to increased use of these agents.

P044Electronic monitoring of psoriasis outcomes andgoals in practice: development and introduction ofa standard dataset and a digital managementsystemM. Augustin,1 J. Wimmer,2 M. Otten,2 V. Djamei,3

A. Navarini4 and M.A. Radtke21Institute and German Center for Health Services Research in Dermatology

and 2CVderm, University Medical Center of Hamburg, Hamburg, Germany;3Swiss4ward Germany, Hamburg, Germany and 4Department of

Dermatology, University of Z€urich, Z€urich, SwitzerlandOutcomes measurement and treatment goals are major com-

ponents of modern psoriasis management in practice. How-

ever, full electronic monitoring and documentation systems

are rare. The objective of the current project was to develop a

platform of electronic devices for the management of clinical

and patient-reported outcomes in psoriasis, including apps for

smartphones, tablets and clinical electronic records. The sys-

tem needed to be compatible with German drug regulations

and the regional legal framework. A digital patient manage-

ment system was to be integrated. As a methodological basis,

the selection of outcomes instruments was based on a system-

atic literature review involving an interdisciplinary team of

experts and patients. The group was comprised of the German

national conference on psoriasis, representing more than 1000

dermatologists, as well as patient groups nationwide. Major

selection criteria of outcomes were validity, feasibility and

representation of different outcomes areas in practice. Consen-

sus of instruments was achieved by a Delphi process, followed

by a second consensus round on relevant clinical thresholds

and end points. The final set of outcomes was tested in

selected centres for feasibility, patient acceptance and technical

performance. The technical solution was provided by Swis-

s4ward Germany, a technology company for digital solutions

in dermatology. All development steps were cross-validated

with conventional clinical routine data. The electronic out-

comes set included Psoriasis Area and Severity Index, body

surface area, Dermatology Life Quality Index and Patient Bene-

fit Index, as well as patient treatment satisfaction and,

optionally, a grid body surface permitting patients to mark the

body areas affected. Other facultative instruments were

included. For the identification of disease-controlled days, an

electronic diary was developed and validated, which measures

continuous patient-reported data. For each instrument, a series

of electronic documentation systems was developed. Finally, a

solution on the management of outcomes was achieved by

monitoring relevant patient outcomes in an electronic switch-

board, enabling continuous recording of the patient outcomes

and controlling the achievement of predefined treatment out-

comes. In the first testing, the electronic documentation and

management system showed good technical properties and

was well accepted by patients. The patient education tool

markedly increased patient satisfaction and adherence. In con-

clusion, the electronic documentation system and the resulting

digital toolbox are feasible and beneficial technologies for the

improved management of psoriasis in practice. Areas of use

included routine patient records, patient registries and clinical

trials.

P045Real-world data identify reasons for biologicalswitching in patients with psoriasisJ. Robinson and L. PriceSpherix Global Insights, Exton, PA, U.S.A.A retrospective patient chart review of over 1000 patients with

psoriasis was conducted in August 2017 by an independent

healthcare market research firm that specializes in tracking

biological uptake in various autoimmune conditions including

psoriasis and psoriatic arthritis. Over 200 U.S. dermatologists

in clinical practice conducted an in-depth review of patients

they had recently switched from one biological or apremilast

to a different agent. To qualify, patients had to have been

switched to another biological or apremilast within the past

3 months The audit was compliant with the Health Insurance

Portability and Accountability Act and conformed to require-

ments under the Safe Harbor Act. Additionally, participating

dermatologists completed a questionnaire about their practice

and their opinions about the use of biologics and small mole-

cules in psoriasis. These data were integrated with the patient

chart data to uncover differences between reported treatment

approaches and actual patient management. The aim of the

study was to uncover the clinical and nonclinical triggers for

switching between biological therapies. The study further

sought to assess the common characteristics of patients being

treated with apremilast, antitumour necrosis factor (anti-TNF)

agents, interleukin-17 inhibitors, ustekinumab and the most

recently approved agent, guselkumab. The study also overlays

key points in time: time since psoriasis diagnosis, time since

first exposure to biological or apremilast and time on prior

agent before switch. The analysis of the data will be complete

in September 2017. The authors hypothesize the following:

(i) when insurance mandates are the primary reason for the

switch, TNF cycling is more likely; (ii) the use of a non-TNF

biologic is reserved for later lines of therapy and for patients

with more severe disease, as assessed by the combination of



body surface area affected, comorbid conditions and

Physician’s Global Assessment; (iii) the use of guselkumab will

primarily displace ustekinumab; (iv) the use of industry-spon-

sored patient assistance programmes is more prevalent among

patients switched to recently introduced products; and (v)

most patients treated with apremilast do not have prior expo-

sure to biological agents and, when switching to apremilast

from a biologic, it is commonly the result of the patient’s

desire for an oral agent or in response to a safety concern

with biological treatment.

P046Comanagement with rheumatologists for patientswith psoriatic arthritis receiving treatment with abiological agent or apremilastJ. Robinson and L. PriceSpherix Global Insights, Exton, PA, U.S.A.A retrospective patient chart review of 1008 patients with pso-

riatic arthritis (PsA) who underwent a switch from one bio-

logical agent or apremilast to another biologic within the

most recent 3 months was conducted in March 2017 by an

independent healthcare market research firm. The aim of the

study, which was completed with the collaboration of 200

U.S. rheumatologists, was to understand current practice man-

agement of patients with PsA and the specific clinical and non-

clinical reasons for therapy changes. The audit was compliant

with the Health Insurance Portability and Accountability Act

and was completed by the treating rheumatologist using an

online, secure audit form. In addition to the patient variables

collected, the project also included a survey of the participat-

ing rheumatologists about their practices and their approach

to PsA patient management. Of interest, 72% of the rheuma-

tologists expressed agreement with the statement ‘I wish der-

matologists would refer PsA patients to me sooner than they

typically do’. Upon analysing the patient records, it was

revealed that most of the patients with PsA were originally

referred by primary care physicians, but more than one in five

were referred by dermatologists. Among those referred by

dermatologists, close to one-third had been previously treated

with a biological agent or apremilast. Furthermore, among

those patients previously treated, the vast majority were

switched to a different agent within the first 3 months of see-

ing a rheumatologist. When asked about ongoing comanage-

ment for the patients who were referred by dermatologists, in

two-thirds of the cases, the rheumatologists reported that they

are the primary physician managing the biologic, and in only

about 20% of the cases did they describe the role between the

dermatologist and themselves as equal. When analysing the

reasons for biologic switching, unsurprisingly, a desire for

increased efficacy in the arthritic disease components was the

most common reason. However, in 14% of the cases, rheuma-

tologists made the switch based on a desire for improvements

in skin efficacy, underscoring rheumatologists’ willingness to

manage both aspects of the disease independently of dermatol-

ogy input. When queried about the preference for using a

biologic in PsA that also has an indication in psoriasis, the

group was largely divided, with one-third reporting that they

are less inclined to use agents that do not have a dual indica-

tion, and another one-third claiming this is not important. In

conclusion, the data suggest that once patients are referred

from dermatologists to rheumatologists the management of

biological therapy is likely to be more commonly directed by

the rheumatologist.

P047Investigation of the role of IKKe role in thepathogenesis of psoriasisI. Weimar, L. Iversen and C. JohansenAarhus University Hospital, Aarhus C, DenmarkInterleukin (IL)-17A is known to play an essential role in the

pathogenesis of psoriasis. IjBf was recently demonstrated to

be a key protein in the development of psoriasis by mediating

IL-17A-driven effects. However, the exact molecular mecha-

nism by which IL-17A and IjBf mediate their psoriatic effects

is not fully understood. IKKe (encoded by the IKBKE gene) is

known to be a critical regulator of IL-17A-mediated signalling.

Interestingly, IKKi was recently demonstrated to play an

important role in the recruitment of neutrophils in IL-17A-

induced inflammation. Moreover, IKKi is involved in the regu-

lation of IjBf expression. Thus, the purpose of this study was

to elucidate the role of IKKe in the pathogenesis of psoriasis.

The methods used in this study included culturing of primary

human keratinocytes, small interfering (si)RNA transfection in

order to knockdown IKKe, quantitative polymerase chain reac-

tion, Western blotting, and haematoxylin and eosin staining.

In addition, the imiquimod-induced psoriasis-like skin inflam-

mation model was used. The mRNA expression of IKBKE was

demonstrated to be significantly increased in skin biopsies

obtained from lesional psoriatic skin compared with both

nonlesional psoriatic skin and normal skin from healthy vol-

unteers. Using siRNA to knockdown IKKe in cultured human

keratinocytes treated with IL-17A and/or tumour necrosis fac-

tor-a revealed that IKKe was involved in the regulation of

specific psoriasis-associated genes including CCL20, DEFB4,

NFKBIZ and CXCL1. To explore further IKKe in the pathogenesis

of psoriasis, the imiquimod-induced psoriasis-like skin inflam-

mation model was applied to IKKe-deficient and wild-type

mice. However, IKKe deficiency was not found to reduce imi-

quimod-induced psoriasis-like skin inflammation as measured

by ear thickness, histological evaluation and expression of

specific psoriasis-associated genes. Taken together, our data

show increased IKBKE mRNA expression in psoriatic skin, as

well as involvement of IKKe in the expression of specific pso-

riasis-associated genes in human keratinocytes. This indicates

that IKKe may play a role in the pathogenesis of psoriasis.

However, this was not substantiated by the results obtained

using the imiquimod-induced psoriasis-like skin inflammation

model in genetically modified mice.





from gene to clinic

95ABSTRACTS

P048The interleukin-17A/F heterodimer regulatespsoriasis-associated genes through IjBfT. Bertelsen, C. Johansen and L. IversenDepartment of Dermatology, Aarhus University Hospital, Aarhus C, DenmarkAntagonists of interleukin (IL)-17 have proven to be highly

effective in the treatment of psoriasis; however, the under-

lying molecular mechanisms involved in the pathogenesis of

psoriasis are not fully understood. Recently, we presented evi-

dence that IjBf (encoded by the NFKBIZ gene) is a key regula-

tor in the development of psoriasis through its role in

mediating IL-17A- and IL-17F-driven effects. IL-17A and

IL-17F are both increased in the skin of patients with psoriasis

and can exist as homodimers or heterodimers. Like IL-17A/A

and IL-17F/F, the IL-17A/F heterodimer is produced by a

variety of immune cells and signals through the same recep-

tors. Based on these facts we hypothesized that the IL-17A/F

heterodimer mediates the regulation of psoriasis-associated

genes through IjBf. The aim of this study was to characterize

the role of the IL-17A/F heterodimer in the regulation of

NFKBIZ expression and in the regulation of psoriasis-associated

genes through IjBf. The methods used in this study were the

culturing of normal human keratinocytes from four to six

donors stimulated with IL-17A/F and tumour necrosis factor

(TNF)-a; small interfering (si)RNA transfection targeting IjBfand quantitative polymerase chain reaction. Statistical analysis

testing for normal distribution was conducted, and a two-way

repeated-measures ANOVA or Friedman test was applied accord-

ing to distribution. For multiple comparisons with control

group the Holm–�Sid�ak or Dunn’s method was applied. Proba-

bility of P < 0.05 was regarded as significant. We demon-

strated that stimulation with the IL-17A/F heterodimer

significantly induced NFKBIZ expression in cultured normal

human keratinocytes. IL-17A/F alone or in combination with

TNF-a significantly induced the mRNA expression of NFKBIZ

after 1.5, 3, 6 and 24 h of stimulation. We found that the

IL-17A/F-mediated induction of NFKBIZ mRNA expression

reached its highest level after 1.5 h of stimulation, and that

IL-17A/F combined with TNF-a increased the induction of

NFKBIZ additionally. Furthermore, we investigated the effect of

IL-17A/F, TNF-a and their combination on NFKBIZ expression

at different concentrations of stimuli. At concentrations of 10,

100 and 1000 ng mL�1, IL-17A/F combined with TNF-a sig-

nificantly induced the mRNA expression of NFKBIZ in a dose-

dependent manner. Moreover, silencing IjBf by siRNA

revealed that IjBf is a key regulator of IL-17A/F heterodimer-

inducible psoriasis-associated genes, including DEFB4, S100A7,

CCL20, CXCL8 and CHI3L1. In conclusion, we present IjBf as a

novel key regulator of the IL-17A/F heterodimer-driven effects

in psoriasis. Thus, antagonists to IjBf could potentially pro-

vide a more targeted approach for treating psoriasis, as well as

for treating other inflammatory and immune-mediated dis-

eases for which IL-17-targeting drugs have proven to be

highly effective.

P049The psoriasis-associated interleukin-17A inducesand cooperates with interleukin-36 cytokines tocontrol keratinocyte differentiation and functionC. Pfaff, Y. Marquardt, D. Kluwig, K. Fietkau,B. L€uscher and J. BaronUniklinik RWTH Aachen, Aachen, GermanyPsoriasis is a T helper 17-driven inflammatory disease affecting

a significant proportion of the world population. Although

interleukin (IL)-17A has been identified as a key cytokine in

the pathogenesis of psoriasis, the molecular consequences of

IL-17A signalling are only partially understood. Therefore we

investigated the effects of IL-17A on downstream molecules

and on the formation and functionality of the skin barrier in

human organotypic three-dimensional (3D) skin equivalents.

We used psoriasis models developed with normal human epi-

dermal keratinocytes (NHEKs) and dermal fibroblasts from

psoriatic lesions of patients and control models containing

cells from healthy donors. Stimulation with IL-17A led to a

defective differentiation of keratinocytes in both models. In

agreement with this phenotype, IL-17A interfered with the

expression of genes encoding structural proteins, which are

important for epidermal differentiation. In addition, antimi-

crobial peptides (AMPs), including human b-defensins and

members of the S100 protein family, are induced, resulting in

a strengthening of the chemical barrier. Finally, we observed

that cytokines, including IL-36 family members, were deregu-

lated upon IL-17A stimulation. We speculated that the IL-17A

effects were at least in part mediated by the induction of

IL-36 cytokines in keratinocytes. Functionally similar to

IL-17A, active IL-36 interfered with keratinocyte differentia-

tion in 3D models and induced the expression of genes

encoding different AMPs. The molecular analysis revealed

strong cooperative effects of these two cytokines in activating

target genes dependent on proteolytic processing of IL-36. In

NHEKs and 3D models we could show that IL-36 cytokines

are produced and secreted upon IL-17A stimulation and that

these proteins are unprocessed and therefore almost inactive.

We were able to activate the released IL-36c with the addition

of activated neutrophil supernatants or recombinant neutrophil

elastase. In both approaches we could detect an increased

expression of genes encoding AMPs and IL-36 cytokines. In

addition, active IL-36c can also induce the expression of

IL-17C and seems to be part of a feed-forward loop. This sug-

gests an amplification cycle that involves IL-17, IL-36 and acti-

vating proteases, providing a molecular explanation for a

persistent psoriatic phenotype. In conclusion, we found that

IL-17A disturbed differentiation in control and psoriasis 3D

skin models. The analysis of the downstream consequences

showed that IL-36 cytokines are produced but need to be

activated via neutrophil proteases to enhance the IL-17A

effects in a synergistic manner.



P050Investigation of the efficacy and safety of acitretintreatment in children with pustular psoriasisX. Zhang, J. Liang and C. LiInstitute of Dermatology, Guangzhou Medical University, Guangzhou, ChinaA retrospective study was undertaken in 15 children with pus-

tular psoriasis (nine boys and six girls). Their mean age was

3.4 � 2.9 years (range 5 months to 9 years). The average

duration of disease was 1.0 years. Ten (67%) of our patients

have generalized pustular psoriasis (GPP) (five boys and five

girls), three (20%) have with palmoplantar pustulosis (PPP)

(three boys) and two (13%) have acrodermatitis continua of

Hallopeau (ACH) (one boy and one girl). They received aci-

tretin in doses of 0.6–1.0 mg kg�1 per day for 4–6 weeks,

then a transition dose of 0.2–0.4 mg kg�1 per day for 4–6 weeks and a maintenance dose of 0.2–0.3 mg kg�1 per day.

We defined excellent response as > 90% clearance of the skin

lesions, good response as 60–90% clearance, moderate

response or improvement as 30–60% clearance, and poor

response as < 30% clearance. The initial treatment dose was

0.6–1.0 mg kg�1 per day for 4–6 weeks, followed by transi-

tion to a dose of acitretin of 0.2–0.4 mg kg�1 per day for a

further 4–6 weeks. The acitretin dose was then adjusted

according to the patients’ clinical responses and side-effects. In

five cases of GPP with tonsillitis and fever, we aimed to con-

trol the infection by concomitant short-term therapy with azi-

thromycin 10 mg kg�1 per day for 4 days. The tonsillitis has

improved in 5 days, and the fever decreased in 3 days, with

body temperature reaching the normal range for all of the five

cases within a week. The 10 cases with GPP, three cases with

PPP and one case of ACH (93%,14 of 15) showed good-to-

excellent response, new pustule formation mostly ceased in

3 days and the skin lesion remission started in 5–7 days. The

acitretin therapy resulted in complete resolution of the skin

lesions within 4–6 weeks for all of those cases, and one case

with ACH (7%) resistant to acitretin therapy exhibited moder-

ate response. When the skin lesions had resolved completely

with the disease under control, acitretin was decreased to a

maintenance dose of 0.2–0.3 mg kg�1 per day for around

6 months. However, one patient with GPP had a relapse when

she ceased acitretin by herself because her skin lesion was in

complete remission within 2 months, but retreatment was still

effective. Overall, 80% (12 of 15) of patients had clinical

side-effects, but these were generally mild and transient. The

most frequently reported acitretin treatments in patients with

pustular psoriasis were dry skin (67%, 10 of 15), itching

(27%, four of 15), cheilitis (20%, three of 15) and dry

mouth (7%, one of 15). Side-effects are mainly dose depen-

dent and may be reduced or avoided by using a lower dose of

therapy and performing routine monitoring.

P051Real-world use of fumaric acid esters in psoriasis:results from the British Association ofDermatologists Biologic Interventions Register(BADBIR)K.J. Mason,1 M. Lunt,1 H.J. Hunter,1,2 Z.K. Jabbar-Lopez,3 B. Kirby,4 C.E. Kleyn,1,2 S. Kreppel,2

K. McElhone,1 N.J. Reynolds,5,6 R.B. Warren12 andC.E.M. Griffiths1,2 on behalf of the BADBIR StudyGroup7

1The University of Manchester, Manchester, U.K.; 2Salford Royal NHS

Foundation Trust, Salford, U.K.; 3King’s College London, London, U.K.;4St Vincent’s University Hospital, Dublin, Ireland; 5Newcastle University,

Newcastle upon Tyne, U.K.; 6Newcastle Hospitals NHS Foundation Trust,

Newcastle upon Tyne, U.K. and 7British Association of Dermatologists,

London, U.K.There is a dearth of published data on the real-world use of

fumaric acid esters (FAEs) to treat psoriasis in the U.K. and

Republic of Ireland. The aim of this study was to describe the

survival, effectiveness and safety profile of FAEs in clinical

practice. BADBIR is a web-based pharmacovigilance register of

patients with psoriasis from 156 dermatology centres in the

U.K. and Republic of Ireland exposed to conventional systemic

and/or biological therapies. Biologic-naive patients registering

on FAEs, or who were exposed to them at follow-up, were

included in the analysis. Drug survival was calculated from the

time of initiating FAE to stopping or censor at the last follow-

up, discounting any temporary cessations of 90 days or less.

For effectiveness, baseline Psoriasis Area and Severity Index

(PASI) was defined as a value of 5 or more within 12 months

prior to initiating FAEs; 6- and 12-month PASI values were

identified between 4–8 months and 10–14 months after initi-

ating therapy, respectively. The proportion of patients achiev-

ing ≥ 75% reduction in PASI (PASI 75) at 6 and/or

12 months was calculated. Adverse events (AEs) reported prior

to stopping FAEs were examined, and were coded according

to the Medical Dictionary for Regulatory Activities. Overall

572 patients (median age 43 years; 58% male) with a

prospective exposure to FAEs were identified, of whom 413

(72%) discontinued during follow-up; 484 (85%) patients

initiating FAEs had previous exposure to other systemic thera-

pies. The discontinuation rate of FAE at 12 months was 53%,

with 25% stopping for AEs, 17% for ineffectiveness and 9%

for other reasons. In total 137 patients (24%) were included

in the effectiveness analysis. The median absolute change in

PASI (interquartile range) was �6.6 (�10.2 to �1.7) at

6 months, and �7.7 (�10.9 to �3.7) at 12 months. PASI 75

was achieved by 28% patients at 6 months, 41% at 12 months

and 18% at both 6 and 12 months. In total, 604 AEs were

reported for 306 patients during FAE exposure. The most

common AEs were 152 (25%) gastrointestinal disturbances,

71 (12%) instances of flushing, 63 (10%) lymphocytopenia

and 52 (9%) psoriasis exacerbations (FAE ineffectiveness). In

conclusion, 53% patients discontinued FAEs in the first

12 months, largely due to AEs or ineffectiveness. The most

common AEs were gastrointestinal disturbances and flushing.





from gene to clinic

97ABSTRACTS

Only 21% patients maintained PASI 75 at 6 and 12 months.

These data provide valuable insight for clinicians and patients

considering FAEs for psoriasis.

P052A real-world comparison of effectiveness andsafety outcomes between clinical trial-eligible and-ineligible patients in the British Association ofDermatologists Biologic Interventions Register(BADBIR)K.J. Mason,1 J.N.W.N. Barker,2 C.H. Smith,2

P.J. Hampton,3 M. Lunt,1 K. McElhone,1

R.B. Warren,1,4 Z.Z.N. Yiu,1,4 C.E.M. Griffiths,1,4

A.D. Burden5 and on behalf of the BADBIR StudyGroup6

1The University of Manchester, Manchester, U.K.; 2King’s College London,

London, U.K.; 3Newcastle Hospitals NHS Foundation Trust, Newcastle upon

Tyne, U.K.; 4Salford Royal NHS Foundation Trust, Salford, U.K.; 5Royal

Infirmary of Edinburgh, Edinburgh, U.K. and 6British Association of

Dermatologists, London, U.K.There is preliminary evidence that patients with psoriasis eligi-

ble for clinical trials of biologics are not representative of real-

world patients. The aim of this study was to determine

whether patients enrolled in BADBIR identified as eligible or

ineligible for clinical trials differed in effectiveness and safety

profiles. BADBIR is a web-based pharmacovigilance register of

patients with psoriasis from 156 dermatology centres in the

U.K. and Republic of Ireland exposed to conventional systemic

and/or biological therapies. Patients with at least 6 months of

follow-up who registered on Enbrel (n = 1509), Humira

(n = 4000) or Stelara (n = 1627) were included in the analy-

sis. Eligibility criteria were extracted from phase III trials sub-

mitted for licensing; additional sources (amgentrials.com;

clinicaltrials.gov; clinical study reports; related manuscripts)

were reviewed for eligibility criteria. Baseline Psoriasis Area

and Severity Index (PASI) values (recorded within 6 months

prior to initiating therapy) were subtracted from PASI values

at 12 months (recorded 10–14 months after initiating ther-

apy) to calculate the median absolute change. Incidence rate

ratios (IRRs) were calculated between the eligibility categories

for the total number of serious adverse events (SAEs) reported

within 12 months of initiating therapy. The following cate-

gories were identified: eligible (Enbrel 56%, Humira 56%,

Stelara 46%), ineligible (Enbrel 24%, Humira 7%, Stelara

24%), insufficient baseline PASI (Enbrel 10%, Humira 29%,

Stelara 23%) and missing baseline PASI (Enbrel 10%, Humira

8%, Stelara 7%). The median absolute change in PASI (in-

terquartile range) at 12 months for ineligible patients [Humira

�11.5 (�15.5 to �8.6), Stelara �11.5 (�17.0 to �8.0)] was

significantly smaller than for eligible patients: �14.4 (�19.3

to �10.9) and �14.4 (�18.7 to �11.2), respectively. There

was no significant difference in median absolute change in

PASI for Enbrel patients at 12 months [eligible �10.3 (�14.3

to �6.7), ineligible �10.5 (�14.7 to �6.7)]. Patients with

an insufficient baseline PASI reported a significantly smaller

median absolute change at 12 months than eligible patients.

SAE rates were highest in the ineligible patients, with signifi-

cantly higher IRR than eligible patients: IRR (95% confidence

interval), Enbrel 1.9 (1.4–2.6); Humira 2.0 (1.5–2.6); Stelara2.8 (2.1–3.8). No differences in SAE rates were detected for

ineligible patients in either baseline PASI category when com-

pared with eligible patients. In conclusion, in the first

12 months of treatment in BADBIR, patients ineligible for

clinical trials for Enbrel, Humira and Stelara had lower effec-

tiveness and higher SAE rates than those who would be eligi-

ble. Thus, clinical trial findings are not representative of real-

world patients.

P053Guselkumab treatment provided higher frequencyof complete skin clearance compared withadalimumab treatment among patients withmoderate-to-severe plaque psoriasisP. Foley,1 M. Song,2 Y.-K. Shen,2 Y. You,2 Y. Wasfi2

and C.E.M. Griffiths31The University of Melbourne, St Vincent’s Hospital, Melbourne and Skin &

Cancer Foundation Inc., Carlton, Australia; 2Janssen Research & Development,

LLC, Spring House, PA, U.S.A. and 3The University of Manchester,

Manchester Academic Health Science Centre, Manchester, U.K.The rates of complete skin clearance associated with guselku-

mab vs. placebo and adalimumab treatment were assessed in

the VOYAGE 1 and VOYAGE 2 clinical trials. In the phase III,

randomized, double-blind, placebo/active comparator-con-

trolled VOYAGE 1 (n = 837) and VOYAGE 2 (n = 992) trials,

patients (≥ 18 years) had plaque psoriasis for ≥ 6 months,

Investigator’s Global Assessment (IGA) scores ≥ 3, Psoriasis

Area and Severity Index (PASI) scores ≥ 12 and ≥ 10% body

surface area involvement, and were candidates for systemic

treatment or phototherapy. Patients were randomized to

guselkumab 100 mg at weeks 0, 4 and 12 than every

8 weeks; placebo at weeks 0, 4 and 12 followed by guselku-

mab 100 mg at weeks 16 and 20 then every 8 weeks; or adal-

imumab 80 mg at week 0, 40 mg at week 1 and 40 mg

every 2 weeks through week 47 (VOYAGE 1) or week 23

(VOYAGE 2). Pooled efficacy, assessed by 100% improvement

in PASI (PASI 100), IGA 0 and Psoriasis Symptoms and Signs

Diary (PSSD) symptoms/signs = 0 (absent signs/symptoms)

from VOYAGE 1 and VOYAGE 2 through week 24 are pre-

sented in this analysis. As early as week 8, a higher proportion

of guselkumab-treated patients achieved PASI 100, IGA 0 and

PSSD signs and symptom scores of 0 vs. placebo. At week 16,

a notable separation between the proportions of patients

achieving these end points in the guselkumab and adalimumab

groups was observed, and the difference was significant at

week 24. In conclusion, guselkumab provided higher rates of

skin clearance, as assessed by PASI 100, IGA 0 and PSSD

symptoms/signs = 0 responses, than adalimumab through

week 24 and placebo at week 16.



P054Antibodies to guselkumab are not associated withreduction in clinical response or development ofinjection-site reactions in patients with moderate-to-severe plaque psoriasisY. Zhu,1 J.C. Marini,1 Y. Wasfi,1 B. Randazzo,1,2

Y.-K. Shen,1 S. Li1 and H. Zhou1

1Janssen Research & Development, LLC, Spring House, PA, U.S.A. and2Department of Dermatology, University of Pennsylvania School of Medicine,

Philadelphia, PA, U.S.A.The aim of this study was to assess the immunogenicity of

guselkumab, an anti-interleukin-23 monoclonal antibody, and

its association with pharmacokinetics (PK), efficacy and injec-

tion-site reactions (ISRs) in patients with moderate-to-severe

plaque psoriasis. In two pivotal phase III studies (VOYAGE 1

and 2, with identical study designs through week 24), patients

were randomized to receive subcutaneous administrations of

guselkumab 100 mg (weeks 0 and 4 then every 8 weeks;

n = 825 total); placebo then guselkumab (n = 422 total) or

adalimumab (n = 582 total). Serum samples were collected at

selected time points up to week 48. Antidrug antibodies

(ADAs) against guselkumab were detected using a validated,

sensitive and drug-tolerant electrochemiluminescence

immunoassay method. Serum guselkumab concentrations (sys-

temic exposure), Investigator’s Global Assessment (IGA) and

Psoriasis Area and Severity Index (PASI) responses and ISRs

were evaluated as PK, efficacy and safety end points, respec-

tively. Of 1361 patients who received guselkumab and had

post-treatment serum samples evaluable for ADA, the overall

incidence of ADA up to week 48 was 6.1% (n = 83), with

predominantly low titres (≤ 1 : 160). Only seven of 83

patients had antibodies that were able to neutralize the bioac-

tivity of guselkumab in vitro. No apparent impact of ADAs on

systemic exposure was observed between ADA-positive

and -negative patients (between-patient comparison), before

and after the development of ADA (within-patient compar-

ison), or by the time (sooner or later) when ADAs were

detected. Of the 58 ADA-positive patients who were evaluable

for the effect of ADA on systemic exposure, 21 had numeri-

cally lower, 25 had numerically higher and 12 had numeri-

cally similar serum guselkumab concentrations after the

formation of ADAs. The development of ADAs was not associ-

ated with a reduction in efficacy. In patients randomized to

guselkumab with available data, 48 (89%) of 54 ADA-positive

patients and 637 (83.3%) of 765 ADA-negative patients

achieved IGA 0 or 1 at week 28. Only six (1.5%) of 388

guselkumab injections in ADA-positive patients and 41 (0.7%)

of 6118 guselkumab injections in ADA-negative patients were

associated with ISRs. In conclusion, following subcutaneous

administrations of guselkumab in patients with moderate-to-severe

plaque psoriasis, the incidence of ADAs was low. The develop-

ment of ADAs to guselkumab was not associated with reductions

in systemic exposure or efficacy, or development of ISRs.

P055Psoriasis Longitudinal Assessment and Registry(PSOLAR): description of demographic data fromthe Greek population upon full enrolmentV. Chasapi,1 C. Antoniou,2 D. Rigopoulos,3

A. Roussaki-Schulze,4 D. Ioannides,5 I. Bassukas,6

W. Langholff7 and E. Soura81State Clinic of Dermatology-Venereology, ‘Andreas Sygros Hospital, Athens,

Greece; 21st Department of Dermatology-Venereology, Medical School,

National and Kapodistrian University of Athens, ‘Andreas Sygros Hospital’,

Athens, Greece; 32nd Department of Dermatology Venereology, Medical

School, National and Kapodistrian University of Athens, Αttikon GeneralUniversity Hospital, Athens, Greece; 4Department of Dermatology-

Venereology, University of Thessaly, University General Hospital Larissa,

Placebo Guselkumab Adalimumab

Patients randomized at week 0 422 825 582

Week 8PASI 100 1/422 (0.2%) 84/825 (10.2%) 46/582 (7.9%)

IGA 0 1/422 (0.2%) 143/825 (17.3%) 67/582 (11.5%)PSSD 0

Symptoms 0 80/658(12.2%) 29/473(6.1%)Signs 0 44/659(6.7%) 16/475(3.4%)

Week 16PASI 100 3/422 (0.7%) 292/825 (35.4%) 108/582 (18.6%)

IGA 0 4/422 (0.9%) 372/825 (45.1%) 159/582 (27.3%)PSSD 0

Symptoms 1/327 (0.3%) 179/658 (27.2%); P < 0.001 75/473(15.9%); P < 0.001Signs 0 136/659 (20.6%); P < 0.001 53/475 (11.2%); P < 0.001

Week 24PASI 100 – 365/825 (44.2%) 149/582 (25.6%)

IGA 0 – 430/825 (52.1%) 176/582 (30.2%)PSSD 0 –Symptoms – 234/658 (35.6%) 104/473 (22.0%); P < 0.001Signs – 187/659 (28.4%) 74/475 (15.6%); P < 0.001





from gene to clinic

99ABSTRACTS

Larissa, Greece; 51st Department of Dermatology, Aristotle University,

Thessaloniki, Greece; 6Department of Dermatology Venereology, Faculty of

Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece;7Janssen Research & Development, LLC, Spring House, PA, U.S.A. and8Jan-Cil Greece, Athens, GreeceThe aim of this study was to report the baseline demographics

and clinical characteristics of Greek participants enrolled in

PSOLAR. PSOLAR is a multicentre, prospective, longitudinal,

observational study designed to follow patients with psoriasis

≥ 18 years of age, currently receiving or candidates to receive

systemic therapies for psoriasis, for ≥ 8 years. The study gath-

ers information from academic and community settings to

generate real-world data regarding patients with psoriasis and

their respective treatments. Such data include baseline demo-

graphics, medical and family history, economic and social

status, adverse events, disease activity, quality of life and inter-

val therapies (evaluated every 6 months). As of 23 August

2014, PSOLAR had enrolled 10 093 patients from North

America, Latin America and Europe. Greece recruited 121

patients, with a patient retention rate of 71.9% since the time

of enrolment. Baseline characteristics for the Greek subpopula-

tion are mean age 45.4 years (median 43.0), with 47.5% of

patients aged ≥ 45 years and 65.3% male. At enrolment

94.2% of patients presented with plaque-type psoriasis, with a

mean Physician’s Global Assessment (PGA) score of 2 � 1.4;

43.3% of patients presented with a PGA score ≥ 3. The mean

duration of psoriasis since diagnosis was 13.7 � 9.8 years,

and 11.6% of patients reported psoriatic arthritis diagnosed by

a joint specialist. The mean body mass index was

29.3 � 5.3 kg m�2, with 74.6% being overweight or obese.

Overall 66.1% and 56.7% of patients reported current use of

alcohol and tobacco, respectively, and 18.2%, 6.6% and

12.4% of patients presented with hypertension, type 2 dia-

betes and hyperlipidaemia, respectively. The mean affected

body surface area and PGA score at peak disease activity were

46.9 � 24.4% and 3.4 � 0.9, respectively, and 33.9% of

patients were receiving systemic therapy at the time of peak

disease activity (16.9% were receiving ciclosporin, 3.4%

methotrexate, 3.4% adalimumab, 3.4% etanercept and 6.8%

infliximab). At the time of enrolment, 82.6% of patients had

received treatment with a biological agent at some point, with

1.7% having received four, 9.1% three, 19.8% two and 52.1%

one. Other treatments included topical therapy (96.7% topical

corticosteroids), phototherapy (25.6%), retinoids (38%),

ciclosporin (67.8%) and methotrexate (28.1%). The clinical,

baseline and historical features for the Greek subset of PSOLAR

patients were as expected for a moderate-to-severe psoriasis

population. Although 74.6% of patients were overweight or

obese, cardiovascular risk factors was reported only in few. In

addition, most patients had received at least one biological or

systemic treatment prior to the time of enrolment, but only

33.9% were receiving systemic treatment at the time of peak

disease activity.

P056Short-term reasons for withdrawal, and safety ofapremilast as a monotherapy and combinationtherapy for psoriasis in clinical practice comparedwith clinical trials: a multicentre retrospectivestudyA. Ighani,1 J.R. Georgakopoulos,2 N.H. Shear,3,4,5

S. Walsh34,5 and J. Yeung3,4,5,61Faculty of Medicine, University of Toronto, Toronto, ON, Canada;2Schulich School of Medicine and Dentistry, Western University, London,

ON, Canada; 3Division of Dermatology, Department of Medicine, University

of Toronto, Toronto, ON, Canada; 4Sunnybrook Health Sciences Centre,

Toronto, ON, Canada; 5Women’s College Hospital, Toronto, ON, Canada

and 6Probity Medical Research Inc., Waterloo, ON, CanadaApremilast is an oral phosphodiesterase 4 inhibitor approved

for the treatment of plaque psoriasis. The safety profile of this

new drug is primarily limited to data published in randomized

controlled trials (RCTs). The objective of our study was to

estimate the real-world safety and incidence of adverse events

(AEs) leading to withdrawal of apremilast in the treatment of

psoriasis, and to compare these findings with RCT results. A

multicentre retrospective chart review was conducted, which

captured all patients treated with apremilast from November

2014 to July 2017. Patients were permitted to use concurrent

therapies with apremilast. Outcome measurements included

the proportion of patients reporting at least AE and the inci-

dence proportion of AEs leading to withdrawal while taking

apremilast during the first 16 weeks of treatment. Real-world

data were compared with RCT data using Pearson’s v2-test(P ≤ 0.01 considered significant). After screening, 208

patients were included in the analysis. A smaller proportion of

real-world patients experienced at least one AE compared with

RCT patients (real world 122 of 208, 58.7%; RCT 573 of

832, 68.9%; P= 0.005). A greater proportion of real-world

patients discontinued apremilast due to AEs compared with

RCT patients (real world 39 of 208, 18.8%; RCT 44 of 832,

5.3%; P < 0.001). Patients who discontinued treatment due to

AEs reported experiencing an average of 2.1 � 1.2 AEs lead-

ing to withdrawal (range one to five). Of the 122 patients

who experienced an AE during the first 16 weeks of treat-

ment, 32.0% went on to withdraw from treatment due to

AEs, and the average time elapsed before withdrawal was

1.7 � 1.0 months. The most commonly reported AEs leading

to withdrawal included diarrhoea (11 of 208, 5.3%), nausea

(10 of 208, 4.8%), headache (nine of 208, 4.3%), nonspecific

gastrointestinal symptoms (seven of 208, 3.4%), abdominal

pain (five of 208, 2.4%), fatigue (four of 208, 1.9%) and

allergic reaction (three of 208, 1.4%). There were no reports

of tuberculosis reactivation or onset of malignancy leading to

withdrawal. In summary, apremilast is generally a safe medi-

cation for the treatment of psoriasis in the real-world setting,

with AEs being reported in similar proportions to RCTs. How-

ever, the proportion of AEs associated with withdrawal in

clinical practice is greater than that reported in RCTs. The

retrospective nature of the study limits the generalizability of

the findings.



P057A comparison of apremilast monotherapy andcombination therapy for plaque psoriasis in clinicalpractice: a multicentre retrospective studyA. Ighani,1 J.R. Georgakopoulos,2 S. Walsh,3,4,5

N.H. Shear34,5 and J. Yeung3,4,5,61Faculty of Medicine, University of Toronto, Toronto, ON, Canada;2Schulich School of Medicine and Dentistry, Western University, London,

ON, Canada; 3Division of Dermatology, Department of Medicine, University

of Toronto, Toronto, ON, Canada; 4Sunnybrook Health Sciences Centre,

Toronto, ON, Canada; 5Women’s College Hospital, Toronto, ON, Canada

and 6Probity Medical Research Inc., Waterloo, ON, CanadaApremilast is a novel, oral drug approved for the treatment of

moderate-to-severe plaque psoriasis as a monotherapy. In clin-

ical practice, it is also used in combination with other biologi-

cal and systemic agents to manage residual plaque psoriasis

that cannot be adequately controlled with one agent alone.

Here we compare the efficacy and safety of apremilast

monotherapy and combination therapy in the real-world set-

ting. A multicentre retrospective chart review was conducted.

Efficacy was measured as the proportion of patients achieving

≥ 75% reduction from baseline Psoriasis Area and Severity

Index score (PASI 75) or a Physician’s Global Assessment

(PGA) score of 0 (clear) or 1 (almost clear) at 16 weeks.

Baseline PASI scores reported for patients on combination

therapy were collected before the onset of apremilast therapy,

not the onset of concurrent systemic therapy. Safety was mea-

sured as the proportion of patients reporting at least adverse

event (AE) at 16 weeks. Binary logistic regression was used to

assess the association of monotherapy and combination ther-

apy with efficacy and safety outcomes (P ≤ 0.05 considered

statistically significant). A total of 296 charts were screened,

and 148 patients were included for analysis. The apremilast

combination therapy cohort (89 of 148, 60.1%) and

monotherapy cohort (59 of 148, 39.9%) showed similar effi-

cacy and safety outcomes. For efficacy, 44% of monotherapy

patients (26 of 59) and 37% of combination therapy patients

(33 of 89) achieved PASI 75 or PGA 0/1 (P = 0.40). For

safety, 63% of monotherapy patients (37 of 59) and 62% of

combination therapy patients (55 of 89) experienced at least

one AE (P = 0.91). Commonly reported adverse events

included headache (monotherapy 24%, combination therapy

12%; P= 0.075), diarrhoea (monotherapy 15%, combination

therapy 17%; P = 0.80), nausea (monotherapy 19%, combi-

nation therapy 11%; P = 0.21) and weight loss (monotherapy

7%, combination therapy 10%; P = 0.49). In conclusion,

apremilast results in clinically significant reduction of chronic

plaque psoriasis, with primarily mild-to-moderate AEs, as both

a monotherapy and combination therapy in the real world.

Limitations of the project include the retrospective nature of

the study. Based on these findings, physicians may consider

using apremilast as a monotherapy to control chronic plaque

psoriasis or as a combination therapy to manage residual pla-

que psoriasis that is not adequately controlled with another

biological or systemic agent alone.

P058An evaluation of the quality of life, treatments andresources available for patients with psoriasis inCanada: a comparison of biologic and nonbiologicusersA. Ighani1 and M.F. Manolson2,31Faculty of Medicine, University of Toronto, Toronto, ON, Canada;2Canadian Association of Psoriasis Patients, Ottawa, ON, Canada and3University of Toronto, Toronto, ON, CanadaThere is a need to update studies analysing Canadians with

psoriasis, given the introduction of new biological treatments.

Here we evaluate the quality of life, treatments and resources

available for patients with psoriasis using biologics or nonbio-

logics as treatment modalities. An online survey, conducted

from July to September 2016, used the following inclusion

criteria: patients with moderate-to-severe psoriasis on one of

the following treatments: biologic, biosimilar, methotrexate,

ciclosporin, apremilast or phototherapy. Additional criteria for

nonbiologic users included psoriasis covering ≥ 10% of body

or psoriasis on the feet, hands, face or genitals. In total 343

patients (218 biologic users and 125 nonbiologic users) were

included. Overall 84% of nonbiologic users were aware of

biologics, and when evaluating various blinded biological

treatments, 45% of nonbiologic users selected blinded ustek-

inumab as their preferred treatment. More biologic users were

satisfied with their treatment (80%) than nonbiologic users

(48%). Regarding quality of life, 41% of biologic users stated

they felt their best when it came to their psoriasis compared

with 25% of nonbiologic users. More ustekinumab users

(70%) than adalimumab users (28%) said they felt their best

regarding their psoriasis, although adalimumab was more

widely used. In terms of patient resources, 77% of patients

selected websites and 73% selected in-person information as

one of their top five preferred resources. Facebook and Twitter

were least preferred. Only 28% of biologic users compared

with 13% of nonbiologic users mentioned healthcare profes-

sional advice as a resource. More nonbiologic users preferred

websites, online forums and Facebook compared with biologic

users. In conclusion, users of biologics were more satisfied

with their treatment and experienced a more positive impact

on life compared with nonbiologic users. Of the available bio-

logics, blinded ustekinumab was most preferred. Patients pre-

ferred websites and in-person information over social media

(Facebook/Twitter) as resources for psoriasis information.

P059Identification of promising biomarkers to predicttherapeutic response to biologics in psoriasisA. Medeiros,1 L. Grine,1 M. Van Gele,1 P. Spuls2 andJ. Lambert11Ghent University Hospital, Ghent, Belgium and 2Academic Medical Center,

Amsterdam, the NetherlandsBiologics are renowned for their effectiveness, but are used as

the last treatment option for moderate-to-severe psoriasis due

to their costs. Currently, we lack guidelines on how to stratify

patients, leading to treatment failure due to unresponsiveness.





from gene to clinic

101ABSTRACTS

This trial and error is not only frustrating for the patient and

doctor, but is a costly matter as well. Here we report the pre-

liminary results on the identification of biomarkers predicting

the therapeutic response to adalimumab and ustekinumab.

Furthermore, we assessed the robustness of mRNA and pro-

teins as biomarkers. Based on the literature, we selected poten-

tial candidates. Patients were recruited at a university hospital

for treatment with either adalimumab or ustekinumab. Blood

was sampled before the first injection and Psoriasis Area and

Severity Index (PASI) was assessed prior to and 6 months after

treatment (DPASI). mRNA markers were measured with

reverse-transcriptase polymerase chain reaction in whole

blood, and protein markers with Luminex and enzyme-linked

immunosorbent assay in serum. Patients were categorized into

responders (DPASI ≥ 90) and nonresponders (DPASI ≤ 75).

Out of 38 potential mRNA markers, we found a significant

differential expression for IL23R, which was lower in non-

responders to ustekinumab, and for VEGF and GOT2, which

were lower and higher, respectively, in nonresponders to adal-

imumab. At the protein level, 14 markers were investigated.

Factor VII correlated significantly with DPASI in ustekinumab-

treated patients, although there was no significant difference

between nonresponders and responders. For adalimumab, a

significant correlation was found for leptin and interleukin-6

with DPASI. Moreover, both proteins were seen in signifi-

cantly higher levels in the nonresponders. In hindsight, practi-

cal and technical evaluation of the robustness of mRNA and

protein showed that the latter was more convenient. Although

this study pilot is based on a small sample size, we provide

evidence that proteins are more promising than mRNA as

biomarkers, and that it is possible to stratify patients for adali-

mumab or ustekinumab. With the arrival of new biologics,

predictive biomarkers are expedient, warranting further inves-

tigation.

P060Evaluation of carcinogenic risk of psoralen–ultraviolet A (PUVA) vs. retinoid–PUVA in patientswith psoriasisH. Mashaly,1 M. Fathy,1 S. Hamdy1 and O. Shaker21Dermatology Department and 2Medical Biochemistry Department, Faculty of

Medicine, Cairo University, Cairo, EgyptPhotochemotherapy with psoralen–ultraviolet A (PUVA) is one

of the classic treatment modalities for psoriasis. Adding reti-

noids in the form of Re-PUVA is hypothesized to reduce the

possible carcinogenic potential of PUVA. 8-Oxoguanine is

among the most mutagenic oxidative DNA modifiers and

induces replication errors. Our aim was to evaluate the possi-

ble carcinogenic protective effect of adding retinoids to PUVA

in patients with psoriasis. A prospective, randomized, con-

trolled study was performed including 20 patients with psori-

asis who were then randomly divided into two groups: group

A received PUVA therapy and group B received Re-PUVA ther-

apy. Each of the 20 patients received 30 sessions of PUVA

photochemotherapy. Patients from Group B received additional

oral retinoids 2 weeks prior to the start of sessions and until

the end of the PUVA sessions. Serum samples were taken from

each of the 20 patients, before and after the last PUVA session,

and were used to measure the 8-oxoguanine level. A signifi-

cant drop in the Psoriasis Area and Severity Index score was

detected in both groups. However, onset of clinical response

was significantly earlier in the Re-PUVA group (P = 0.037),

together with a significantly lower cumulative dose of UVA

(P= 0.002). A rise of serum level of 8-oxoguanine was

noticed in patients with psoriasis following PUVA therapy,

while a drop of serum level of 8-oxoguanine was noticed fol-

lowing Re-PUVA therapy. Comparing the change of serum

levels of 8-oxoguanine in patients receiving PUVA vs. Re-

PUVA showed a more significant drop of 8-oxoguanine in the

patients receiving Re-PUVA (P= 0.023). Re-PUVA was able to

achieve the same clinical response as PUVA in patients with

psoriasis, but with an earlier onset of clinical response, less

UVA cumulative dose, less DNA damage in the serum, and

hence less carcinogenic potential.

P061Successful treatment of recalcitrant hyperkeratoticpalmoplantar psoriasis with itolizumab: a caseseries of three patientsU. Chakravadhanula1 and B.K. Jha21Vaikhan Hospital, Hyderabad, India and 2Medical Affairs, Biocon Ltd,

Bangalore, IndiaPalmoplantar psoriasis (PP) is a chronic inflammatory skin dis-

ease that is associated with distressful quality of life. The

prevalence of chronic plaque psoriasis in different populations

is 1–3%, whereas PP accounts for 3–4% of all cases of psoria-

sis in most studies. We present a case series of three patients

with PP that responded remarkably to itolizumab. Itolizumab

(Alzumab�) is a novel humanized monoclonal antibody

approved for moderate-to-severe chronic plaque psoriasis. It

downregulates T-cell proliferation induced by activated leuco-

cyte cell adhesion molecules by binding to the extracellular

scavenger receptor cysteine-rich distal domain 1 of CD6 (Kru-

pashankar DS, Dogra S, Kura M et al. Efficacy and safety of ito-

lizumab, a novel anti-CD6 monoclonal antibody, in patients

with moderate to severe chronic plaque psoriasis: results of a

double-blind, randomized, placebo-controlled, phase-III study.

J Am Acad Dermatol 2014; 71: 484–92). Case 1, a 22-year-old

man, presented with a history of localized hyperkeratotic plan-

tar psoriasis with toenail involvement for 2 years. Case 2 is a

42-year-old man with both palms affected for 3 years. It is

essential to mention that the patient did not respond to five

doses of secukinumab (anti-interleukin-17A). Case 3 is a 63-

year-old man who presented with severe palmoplantar

hyperkeratosis, fissuring and 100% involvement of the soles

including the nails. Due to failure of available treatment

modalities, all three patients were screened for infection, neo-

plasm and autoimmunity, which were negative in all cases.

They were started on itolizumab at a dose of 1.6 mg kg�1 (in

250 mL of normal saline over 3 h) fortnightly followed by

maintenance phase of three 4-weekly infusions. All patients

achieved 75% improvement in the Palmoplantar Psoriasis Area



Severity Index after the seventh infusion. The quality of life

significantly improved in all patients. Needless to say, only a

small area of the body is affected in PP or psoriasis of the

palms and soles; however, the symptoms lead to a distressful

and disabling quality of life due to the condition being diffi-

cult to treat. In cases where conventional therapies have failed,

published studies demonstrate that noncytokine biologics,

which act upstream of T-cell proliferation, have been effective

in treating PP; these include alefacept and efalizumab (Lior S,

Grigory K, Pnina S et al. Therapeutic hotline. Alefacept in the

treatment of hyperkeratotic palmoplantar psoriasis. Dermatol Ther

2010; 23: 556–60). In consonance with the efficacy profile of

other upstream acting biologics, namely alefacept and efal-

izumab, itolizumab also resulted in a remarkable response to

PP in the present cases. It can be postulated that itolizumab

immunomodulates the downstream cytokine infiltration in PP

without inhibiting the constitutive expression of lymphocytes,

and thus has a better safety profile. Thus, itolizumab may be a

safe and efficacious treatment option in PP, a difficult-to-treat

variant of psoriasis.

P062Systemic therapy and the risk of nonmelanomaskin cancer among patients in the PsoriasisLongitudinal Assessment and RegistryR. DeShazo,1 R. Soltani-Arabshahi,2 S. Krishnasamy,1

C. Galindo,3 W. Langholff,4 R. Langley,5 S. Kalia,6

S. Fakharzadeh,3 K. Goyal,3 M. St�ahle,7

B. Srivastava3 and G.G. Krueger1

1University of Utah, Salt Lake City, UT, U.S.A.; 2Cleveland Clinic,

Cleveland, OH, U.S.A.; 3Janssen Scientific Affairs, LLC, Spring House, PA,

U.S.A.; 4Janssen Research & Development, LLC, Spring House, PA, U.S.A.;5Dalhousie University, Halifax, NS, Canada; 6University of British

Columbia, Vancouver, BC, Canada and 7Karolinska Institutet, Stockholm,

SwedenPsoriasis is associated with increased risk of nonmelanoma

skin cancer (NMSC), including basal cell carcinoma (BCC) and

squamous cell carcinoma (SCC). Our aim was to determine

the effect of biological therapy on NMSC risk among patients

in PSOLAR, a prospective psoriasis registry for patients eligible

to receive systemic treatment. Data extracted from 23 August

2015 were included. We defined a study population of 6782

PSOLAR patients without a history of NMSC at enrolment who

were prevalent or incident users of biologics (n = 6350) or

methotrexate (MTX, n = 432). The biologics cohort included

infliximab (IFX), etanercept (ETN), adalimumab (ADA) and

ustekinumab (UST). Subcohorts of pooled patients receiving

tumour necrosis factor inhibitors (TNFis; IFX, ETN and ADA;

n = 3727) and UST (n = 2623) patients were also defined for

the secondary objective. Switching of study therapies was

allowed; events falling within any 91-day overlap period were

attributed to both therapies. Incidence rates (IRs) for NMSC

were calculated, and Cox proportional hazard models (using

MTX as the reference) were used to estimate hazard ratios

(HRs) adjusted by covariates relevant to NMSC risk. The treat-

ment cohorts were generally comparable for most baseline

characteristics. Seventy-two new diagnoses of NMSC were

identified [IR 0.37, 95% confidence interval (CI) 0.30–0.47].The IRs and confidence intervals for NMSC, SCC and BCC are

displayed in Table 1a, and hazard ratios by NMSC type are

displayed in Table1b. Biological therapy did not alter the risk

of NMSC. In the secondary analysis, TNFis did not alter the

risk of incident NMSC or BCC compared with MTX, whereas

UST showed significantly lower risk than MTX. The results for

SCC are difficult to interpret due to wide confidence intervals.

The results require further validation in psoriasis populations

with larger numbers of exposed patients.

P063Interleukin-10 regulates skin thickness and scalingin imiquimod-induced psoriasis-like skininflammation in miceX. Xu,1 E. Prens,1 E. Florencia,1 L. Boon,2

P. Asmawidjaja,1 A.-M. Otten-Mus1 and E. Lubberts1

a. Crude incidence rates of NMSC after exposure to biologics or methotrexate

NMSC SCC BCC

Events IR (95% CI) Events IR (95% CI) Events IR (95% CI)

All study (19 261 PY) 72 0.37 (0.30–0.47) 24 0.12 (0.08–0.19) 48 0.25 (0.19–0.33)All biologics (18 480 PY) 61 0.33 (0.26–0.42) 23 0.12 (0.08–0.19) 38 0.21 (0.15–0.28)UST (7900 PY) 15 0.19 (0.11–0.31) 5 0.06 (0.03–0.15) 10 0.13 (0.07–0.24)TNFi (10 580 PY) 46 0.43 (0.33–0.58) 18 0.17 (0.11–0.27) 28 0.26 (0.18–0.38)Methotrexate (781 PY) 11 1.41 (0.78–2.54) 1 0.13 (0.02–0.91) 10 1.28 (0.69–2.38)

b. HRs of NMSC after exposure to biologics or methotrexate

All biologics 0.61 (0.28–1.35) 2.63 (0.31–22.6) 0.42 (0.17–1.01)P = 0.22 P = 0.38 P= 0.054

UST 0.35 (0.14–0.87) 1.37 (0.14–13.5) 0.26 (0.09–0.72)P= 0.023 P = 0.79 P= 0.0095

TNFi 0.81 (0.37–1.80) 3.49 (0.40–30.1) 0.55 (0.22–1.36)P = 0.61 P = 0.26 P = 0.19

IRs are events per 100 person-years.





from gene to clinic

103ABSTRACTS

1Erasmus Medical Center, Rotterdam, the Netherlands and 2Bioceros, Utrecht,

the NetherlandsPsoriasis is an autoimmune skin disease affecting around 0.6–3%of the whole population, with detrimental physical and societal

impacts. Previously we established a psoriasis-like skin inflamma-

tion model in mice using topical application of imiquimod. This

model successfully recaptures most of the critical features of acute

psoriasis, such as keratinocyte hyperproliferation and Munro’s

microabscesses, and shares a similar infiltration profile of various

immune cells. Previous data suggested upregulation of interleukin

(IL)-10 during induction of the imiquimod model, but its role in

this psoriasiform model was not clear. Our aim was thus to inves-

tigate the role of IL-10 in imiquimod-induced psoriasis-like skin

inflammation. Psoriasis-like skin inflammation was induced by

topical application of imiquimod (Aldara) for 5 and 10 days.

Mice were injected intraperitoneally with anti-IL-10 or an isotype

control antibody, or subcutaneously with dexamethasone. The

back skin of mice was scored for up to 10 days using a modified

Psoriasis Area and Severity Index (PASI) score system adapted

from clinical PASI score. Inflammation and skin thickness were

scored histologically. Gene expression and immune cells in the

skin were analysed using quantitative polymerase chain reaction

and flow cytometry, respectively. At day 10, both the skin thick-

ness and scaling score were significantly higher after neutralizing

IL-10 compared with isotype control, and in both groups com-

pared with dexamethasone-treated animals. At days 5 and 10,

haematoxylin and eosin staining confirmed that epidermal thick-

ness was more prominent in anti-IL-10-treated mice than in iso-

type control or dexamethasone-treated mice, with more

profound differences at day 10. Ki-67 staining for proliferating

keratinocytes showed more proliferation at the epidermal basal

layer after neutralizing IL-10. In addition, significantly more infil-

tration of neutrophils was found in skin at day 10. In the early

phase (day 5), IL-23/IL-17 pathway cytokines were more signifi-

cantly upregulated in anti-IL-10 antibody-treated group than in

the isotype control group, while at a late stage (day10) a signifi-

cant upregulation was found in IL-19 and IL-24 expression. IL-10

regulates skin thickness and scaling during psoriasis-like skin

inflammation. Furthermore, our data suggest that IL-10 might

influence psoriatic symptoms through dampening of the IL-23/

IL-17 axis in the early phase and by reducing IL-19 and IL-24

expression at the late stage. This negative feedback signal of IL-10

partially explains the observed decrease of inflammation in imi-

quimod-induced skin inflammation after day 5.

P064The identification of interleukin (IL)-17A+, IL-17RA+

and IL-17RC+ lymphoid and myeloid cells in bloodof treatment-naive early patients and in synovialfluid of established patients with psoriatic arthritisX. Xu,1 N. Davelaar,1 A.-M. Otten-Mus,1

P. Asmawidjaja,1 H. den Braanker,1 J. Hazes,1

R. Bisoendial,1,2 M. Vis1 and E. Lubberts1

1Erasmus Medical Center, Rotterdam, the Netherlands and 2Maasstad

Hospital, Rotterdam, the Netherlands

Interleukin (IL)-17A is a proinflammatory cytokine involved

in the pathogenesis of psoriatic arthritis (PsA). Biologics tar-

geting IL-17A have been approved in clinical treatment of

patients with PsA. However, various cells can produce IL-17A,

and it is not clear which cell types are responsible for IL-17A

production in patients with PsA. Additionally, the expression

of IL-17A receptors, IL-17RA and IL-17RC, on different cell

types is not well defined. In this study, IL-17A-, IL-17RA- and

IL-17RC-positive cells in blood of patients with a first diagno-

sis of PsA with arthritis, and in synovial fluid of patients with

established PsA with active disease were examined. Fresh

blood was taken from first diagnosed disease-modifying anti-

rheumatic drug- and steroid-naive patients with PsA (n = 10)

with arthritis in at least one joint (PsA blood). Diagnoses were

made by rheumatologists according to the CASPAR criteria.

Fresh synovial fluid was obtained from patients with estab-

lished PsA (PsA SF) with active disease (n = 10) and treated

with either methotrexate (n = 3), adalimumab (n = 3) or

nonsteroidal anti-inflammatory drugs (n = 4). Multicolour

flow cytometric analysis was performed on PsA blood and PsA

SF. Different lymphoid and myeloid cell types were IL-17A-

positive in PsA blood of first-diagnosed patients with PsA,

such as CD3+, T-cell receptor (TCR)-cd+, CD4+ and CD8+

lymphoid cells; CD14+ monocytes; and CD15+ FcER1a+ eosi-

nophils. In PsA SF of patients with established PsA, T cells,

neutrophils, natural killer cells and eosinophils were IL-17A

positive. In both groups, no difference in expression of IL-

17RA and IL-17RC was found on CD4+, CD8+,

CD4+ CD45RO+ CCR6�, TCR-cd+ and CD19+ lymphoid cells

compared with the isotype control. In contrast, the expression

of IL-17RA and IL-17RC was increased compared with the iso-

type control on neutrophils and monocytes in PsA blood and

on neutrophils, monocytes, mast cells and eosinophils in PsA

SF. These preliminary data show that not only lymphoid cells

but also specific myeloid cell types may be sources of IL-17A

in PsA. Furthermore, not only lymphoid cells but IL-17RA/

IL-17RC-positive myeloid cells such as monocytes, neutrophils,

mast cells and eosinophils may be potential target cells for

IL-17A. Together, these data suggest a broader, but specific

IL-17A- IL-17RA/RC signalling network among different cell

types involved in the IL-17A-driven pathogenesis of PsA.

P065Distinct and overlapping activities of interleukin(IL)-17A and tumour necrosis factor (TNF) on theexpression of proinflammatory cytokines andmatrix metalloproteinases in psoriatic arthritis:rationale for anti-IL-17A/anti-TNF-a combinationtherapy?X. Xu,1 N. Davelaar,1 A.-M. Otten-Mus,1

P. Asmawidjaja,1 J. Hazes,1 D. Baeten,2 M. Vis,1

R. Bisoendial1,3 and E. Lubberts1

1Erasmus Medical Center, Rotterdam, the Netherlands; 2Academic Medical

Center, Amsterdam, the Netherlands and 3Maasstad Hospital, Rotterdam, the

Netherlands



Tumour necrosis factor (TNF) and interleukin (IL)-17A are

proinflammatory cytokines critically involved in the pathogen-

esis of psoriatic arthritis (PsA). Currently, targeting TNF is the

first choice of biological disease-modifying antirheumatic

drugs (bDMARDs) in PsA. However, up to 30% of patients

receiving anti-TNF monotherapy fail to respond and require

switching to a second TNF inhibitor or bDMARD with a dif-

ferent mode of action. Strategies targeted at neutralizing

IL-17A have been shown to have beneficial effects on skin,

enthesitis, dactylitis and joint inflammation. Here we explore

the effect of neutralizing IL-17A vs. anti-TNF on the expres-

sion of proinflammatory cytokines and metalloproteinases

(MMPs) and whether dual therapy targeting TNF and IL-17A

may have superior activity than treatment with either agent

alone. An allogeneic coculture system was used comprising

synovial-fluid T helper memory cells and synovial fibroblasts

(SFs) derived from patients with active PsA. Anti-CD3/CD28

stimulation was used during culture, and an anti-IL-17A anti-

body (secukinumab), anti-TNF-a antibody (adalimumab) or

their combination was added. PsA-unstimulated synovial T

helper memory cells cocultured with PsA SFs were included as

a control group, along with an isotype antibody control

group. After 72 h, supernatants were harvested for enzyme-

linked immunosorbent assay and cells were lysed for quantita-

tive polymerase chain reaction analysis. Anti-TNF antibody

treatment had no effect on IL-17A, levels and neutralization of

IL-17A did not influence the TNF production in the coculture

system. Both anti-TNF and anti-IL-17A single treatment signif-

icantly inhibited the production of IL-8 and reduced the

mRNA expression of IL-1b. Interestingly, neutralizing IL-17A

resulted in a significant suppression of IL-6 level, which was

not reduced by anti-TNF. Anti-TNF inhibited the production

of MMP-3, and only the combination of anti-TNF and anti-IL-

17A resulted in a significant suppression of MMP-1 levels and

MMP-9 mRNA expression. MMP-13 mRNA expression was

significantly suppressed by anti-TNF but not by anti-IL-17A;

however, neutralizing both IL-17A and TNF showed a

significant improvement in downregulating MMP-13 mRNA

expression compared with single cytokine treatment. More-

over, anti-IL-17A reduced RANK mRNA expression, which

was significantly more suppressed compared with anti-TNF

alone. However, no additive effect was noted for the combi-

nation blocking. Interestingly, only neutralizing both IL-17A

and TNF significantly reduced the mRNA expression of

RANKL. Osteoprotegerin (OPG) mRNA expression was not

influenced by anti-IL-17A and/or anti-TNF treatment. Neutral-

izing IL-17A or TNF in the PsA synovial T-cell–SF coculture

system resulted in overlapping but also distinct effects on

proinflammatory cytokine expression. TNF inhibition mark-

edly suppress different MMPs with mostly an additional effect

upon neutralization of IL-17A. Neutralization of both IL-17A

and TNF is needed to downregulate RANKL expression, which

changes the RANKL/OPG balance. Together, these preliminary

data suggest that dual therapy targeting IL-17A and TNF may

be superior in protecting against erosive arthropathy in PsA

than treatment with either agent alone.

P066Unopposed interleukin (IL)-36 activity promotesclonal CD4+ T-cell responses with IL-17A productionin generalized pustular psoriasisA. Arakawa, S. Vollmer, P. Besgen, B. Summer,P. Thomas, T. Ruzicka and J.C. PrinzLudwig-Maximilians-University, M€unich, GermanyMutations in IL36RN, CARD14 or AP1S3 provide genetic evi-

dence for autoinflammatory aetiology in generalized pustular

psoriasis (GPP). Although GPP has been considered as the

most severe psoriasis variant, the pathogenetic overlap with

psoriasis vulgaris (PV) remains elusive. As PV is a CD8+ T-cell

mediated autoimmune disease, we investigated the role of T

cells in GPP using PV as a disease control. Here we demon-

strate that unopposed Interleukin (IL)-36 signalling may coop-

erate with certain human leucocyte antigen (HLA) class II

alleles to induce antigen-driven T helper (Th)17 responses in

GPP, which are presumably directed against autoantigens in

the absence of exogenous triggers. We analysed eight patients

with GPP to show that deficits in IL36RN function may result

from IL36RN mutations or decreased IL36RN transcription.

Molecular analysis of T-cell receptor (TCR) rearrangements

revealed strong TCR-driven activation signatures in CD8+ T

cells of patients with PV and GPP and identical T-cell clones in

blood and skin lesions, suggesting common pathogenic path-

ways in PV and GPP. Notably, CD4+ T cells of patients with

GPP were characterized by strong autoproliferation, highly

restricted clonal TCR repertoires, identical T-cell clones in

blood and skin lesions, and predominant differentiation into

Th17 cells, whereas TCR-driven CD4+ T-cell activation was

modest in PV. The clonal CD4+ T-cell populations preferen-

tially produced IL-17A, a key mediator in GPP. IL36B substan-

tially enhanced TCR-mediated proliferation of CD4+ T cells

in vitro. Moreover, the patients with GPP showed high occur-

rence of certain HLA-class II alleles, HLA-DQB1*03, HLA-

DQB1*05 and HLA-DRB1*14, in contrast to weak HLA-class II

associations of PV. Thus, CD4+ T-cell involvement clearly dif-

ferentiated GPP from PV. GPP might therefore represent a dis-

ease where autoinflammation promotes CD4+ T-cell-mediated

autoimmunity in the context of HLA-class II-association.

P067Remarkable response of recalcitrant hyperkeratoticpalmoplantar psoriasis to itolizumab: a case reportU. Chakravadhanula1 and B.K. Jha2

1Vaikhan Hospital, Hyderabad, India and 2Medical Affairs, Biocon Ltd,

Bangalore, IndiaPalmoplantar psoriasis (PP) is a chronic inflammatory skin dis-

ease that is associated with distressful quality of life. The

prevalence of PP is 3–4% among all cases of psoriasis in most

studies. We present a case of PP that responded remarkably to

itolizumab. Itolizumab (Alzumab�) is a novel humanized

monoclonal antibody approved for moderate-to-severe chronic

plaque psoriasis. It downregulates T-cell proliferation induced

by activated leucocyte cell adhesion molecules by binding to

the extracellular scavenger receptor cysteine-rich distal domain





from gene to clinic

105ABSTRACTS

1 of CD6 (Krupashankar DS, Dogra S, Kura M et al. Efficacy

and safety of itolizumab, a novel anti-CD6 monoclonal

antibody, in patients with moderate to severe chronic plaque

psoriasis: results of a double-blind, randomized, placebo-

controlled, phase-III study. J Am Acad Dermatol 2014; 71:

484–92). A 42-year man presented at our clinic with PP with

both palms affected for over 3 years. The patient had already

received different treatment modalities including systemic and

biological therapy. His treatment history at another hospital

was as follows: high-potency topical corticosteroids and cal-

cipotriol; topical psoralen ultraviolet A therapy three times a

week for 6 months; and methotrexate 7.5 mg per week asso-

ciated with elevated transaminase values. Biological treatment

taken elsewhere was five doses of secukinumab, and inter-

leukin-17A inhibitor. The patient did not respond to the

aforementioned biological treatment. Also, this patient had a

history of thyrotomy. Due to failure of the aforementioned

treatment modalities, the patient, after screening for infection,

neoplasm and autoimmunity, which were negative, started on

itolizumab at a dose of 1.6 mg kg�1 (in 250 mL of normal

saline over 3 h) fortnightly followed by a maintenance phase

of three 4-weekly infusions. The patient achieved 85%

improvement in the Palmoplantar Psoriasis Area Severity Index

after the seventh infusion. His quality of life index also

improved significantly. Needless to say, only a small area of

the body is affected in PP or psoriasis of the palms and soles;

however, the symptoms lead to a distressful and disabling

quality of life, as this is a difficult-to-treat condition. In cases

where conventional therapies have failed, published studies

demonstrate that noncytokine biologics that act upstream (be-

fore T-cell activation), such as alefacept and efalizumab, have

been effective in treating PP (Lior S, Grigory K, Pnina S et al.

Therapeutic hotline. Alefacept in the treatment of hyperkera-

totic palmoplantar psoriasis. Dermatol Ther 2010; 23: 556–560).Similarly to the efficacy profile of other upstream-acting bio-

logics, namely alefacept and efalizumab, itolizumab also

resulted into a remarkable response to PP in the present stud-

ied case. It can be postulated that itolizumab immunomodu-

lates the downstream cytokine infiltration in PP without

inhibiting the constitutive expression of lymphocytes, thus

showing a better safety profile. Thus, itolizumab may be a safe

and efficacious treatment option in PP, a difficult-to-treat vari-

ant of psoriasis.

P068Effects of methotrexate on treatment and seruminflammatory cytokines in paediatric patients withsevere plaque psoriasisZ. Xu, Y. Gu and Z. WangDepartment of Dermatology, Beijing Children’s Hospital, Capital Medical

University, Beijing, ChinaAlthough the majority of cases of childhood psoriasis can be

managed with various topical agents, a proportion of patients

with severe disease need systemic therapies. Methotrexate

(MTX) is a well-known systemic treatment for severe paedi-

atric plaque psoriasis; however, evidence of its effectiveness

and safety is scarce, and its impact on serum inflammatory

cytokines remains unclear. This study aims to evaluate the

effectiveness of MTX in paediatric severe plaque psoriasis and

to describe changes in serum levels of interleukin (IL)-17A,

IL-23 and tumour necrosis factor (TNF)-a observed during

MTX treatment. The indication for MTX use is baseline Psoria-

sis Area and Severity Index (PASI) ≥ 15 or baseline body sur-

face area ≥ 20%. MTX was given at a single weekly oral dose

of 0.1–0.3 mg kg�1 to 18 paediatric patients with severe pla-

que psoriasis for 24 weeks. The efficacy of MTX was evaluated

by PASI and Children’s Dermatology Life Quality Index

(CDLQI). The levels of IL-17A, IL-23, TNF-a in peripheral

blood at baseline and week 24 were measured by liquid-phase

suspension chip. The PASI of the 18 patients significantly

decreased at weeks 4, 8, 12 and 24 compared with baseline

(30.4 � 8.9 vs. 21.9 � 12.1, t = 2.39; 30.4 � 8.9 vs. 12.9

� 9.6, t = 5.47; 30.4 � 8.9 vs. 4.7 � 3.4, t = 9.92; 30.4 �8.9 vs. 1.8 � 2.2, t = 8.93, all P < 0.05). PASI 75 (≥ 75%

improvement from baseline) was achieved in 12%, 40%, 77%

and 100% of patients at week 4s, 8, 12 and 24, respectively.

The median CDLQI decreased significantly at weeks 12 and

24. After 24 weeks of MTX treatment, the serum concentra-

tions of IL-17A, IL-23, TNF-a were lower than those at base-

line (Z = �2.42; Z = �2.31 and Z = �2.55, respectively, all

P < 0.05).The adverse events included nausea, loss of appetite,

and slightly elevated alanine aminotransferase and aspartate

transaminase. A low dose of MTX is effective and safe for sev-

ere paediatric plaque psoriasis. The serum levels of inflamma-

tory cytokines decline as PASI decreases.

P069Sustained remission in a patient with chronicplaque psoriasis treated with itolizumab: a 4-yearfollow-up experienceS.G. Parasramani,1 G.G. Kunder,2 S.H. Suresh2 andD.R. Pawar21Lilavati Hospital, Mumbai, India and 2Medical Affairs, Biocon, Bangalore,

IndiaA 53-year-old female patient with a history of psoriasis for

12 years was presented to us. On investigation it was found

that she had earlier been treated with topicals and methotrex-

ate. As her baseline Psoriasis Area and Severity Index (PASI)

on presenting to us was 21.8 and she had previously been

treated with the available treatment options she was suggested

to start biologics. The aim for use of biologics was to provide

the patient with quicker relief and long-term sustained

disease-free remission. The biologic of choice here was

itolizumab, a monoclonal anti-CD6 antibody that showed evi-

dence of remission in the phase III trial of the drug (Dogra S,

D SK, Budamakuntla L et al. Long-term efficacy and safety of

itolizumab in patients with moderate-to-severe chronic plaque

psoriasis: a double-blind, randomized-withdrawal, placebo-

controlled study. J Am Acad Dermatol 2015; 73: 331–3). Beforeinitiating the therapy, laboratory parameters of the patient

including serum creatinine, blood urea, liver function tests

and thyroid function tests, along with X-ray chest and



electrocardiogram, were analysed and normal. Tests for HIV,

hepatitis B and hepatitis C, and Mantoux test were negative.

After all the examinations were normal the patient was given

intravenous itolizumab 1.6 mg kg�1 body weight (75 mg in

250 mL of normal saline over 2 h). In total 10 injections

were given over a period of 6 months, followed by mainte-

nance dosing once every 3 months. The patient achieved PASI

90 response (90% improvement from baseline) at the end of

the 6th week (PASI score 1.9) and progressed to PASI 100

(PASI score 0.1) after the completion of 10 doses. In order to

maintain remission the patient is being given maintenance

dosing once every 3 months, and to date continues to main-

tain PASI 90 after 41 weeks of therapy (over 4 years). These

results are in agreement with the phase III studies of itolizu-

mab and have improved the clinical and quality-of-life

parameters of the patient. Thus itolizumab serves as the drug

of choice to maintain disease-free remission in moderate-to-

severe chronic plaque psoriasis.

P070Treat to target in psoriasis: a Belgian attempt todefine a tight control strategy for psoriasismanagementL. Grine,1 S. Segaert,2 J. Lambert,3 M. de laBrassinne,4 P.-D. Ghislain,5 F. Willaert,6 T. Hillary7 andJ. Lambert1

1Ghent University Hospital, Ghent, Belgium; 2University Hospital Leuven,

Leuven, Belgium; 3University Hospital of Antwerp, Antwerp, Belgium;4Centre Hospitalier Universitaire de Li�ege, Li�ege, Belgium; 5Clinical Research

Cliniques Saint-Luc, Brussels, Belgium; 6Erasme University Hospital, Brussels,

Belgium and 7Free University of Brussels, Brussels, BelgiumTreat to target (T2T) is defined as a therapeutic algorithm

designed around well-defined and specific therapeutic targets

in the management of a disease. This concept is characterized

by ‘tight control’, whereby a treatment algorithm is followed

regarding evaluation, assessment and treatment decision. T2T

strategies have gained a lot of interest since their first successes

in rheumatoid arthritis and diabetes. It seems the time has

come to introduce T2T in psoriasis, although many attempts

cannot be readily translated to the Belgian situation. We aim

to redefine a T2T strategy in light of the Belgian real-world

setting, which is currently ongoing. Questioning will be per-

formed through the Delphi technique, to build consensus

using a series of questionnaires to collect data from a panel of

experts. An expert board of Belgian key opinion leaders will

participate in defining a tight control strategy in Belgium. The

initial meetings are about the T2T concept, Belgian regula-

tions, relevant topics that need to be addressed, and introduc-

tion of the Delphi-structured questioning. The key opinion

leaders will be asked to expand the number of experts by pro-

viding names of relevant psoriasis experts to be included as

additional respondents. Next, the Delphi questionnaire will be

developed based on literature review and discussion points

during the meetings by two independent researchers. Answers

will be given on a 11-point Likert-scale; open questions may

be asked to explain the respondent’s rationale. The responses

will be categorized for the second iteration, which will enable

quantification of rationales. Responses will be analysed and a

second questionnaire will be created, including trends (me-

dian and interquartile) of the responses. For the second round,

the adapted questionnaires will be sent to the participants, and

they will be asked to modify or confirm their previous

answers or to specify the reasons for remaining outside the

consensus. Afterwards, a final analysis of the consensus will be

done. The primary outcome of this study will be to reach

consensus on a target specifically for psoriasis in Belgium, in

order to base algorithmic treatment decisions on this target.

Key secondary end points include a treatment algorithm (T2T

strategy) and a protocol for a randomized controlled trial to

evaluate the T2T strategy in Belgium. This study will provide

direct evidence on how Belgian psoriasis experts view the

tight control strategy for psoriasis in light of Belgian reim-

bursement, and whether T2T is feasible in Belgian clinical

practice for increased cost-effective use of current treatments.

P071Retrospective review of psoriasis ustekinumaboutcomes using real clinic data analysed usingstarting Psoriasis Area and Severity Index (PASI)and worst PASI in the preceding 5 years with PASI75 and 90 reportedC. Goodhead and P. HamptonRoyal Victoria Infirmary, Newcastle, U.K.The electronic notes of 114 patients who received ustek-

inumab for chronic plaque psoriasis were reviewed. Baseline

Psoriasis Area and Severity Index (PASI) were calculated using

different methods: (i) starting PASI (on day of first drug

administration) vs. (ii) worst PASI in the preceding 5 years.

Variations with weight and dose were also analysed. Patients

starting ustekinumab between December 2008 and January

2016 were included, and retrospective data were collected

Weight (kg)

Ustekinumab

dose Patients

PASI 90 at3 months using

starting PASI, %


starting PASI, %


worst 5-year PASI, %

PASI < 3 at 3 months

using starting PASI, %

≤ 80 45 mg 30 19 46 54 46

80.1–100 45 mg 28 18 39 57 4680.1–100 90 mg 18 35 65 71 59

100.1–120 90 mg 23 18 41 55 32> 120.1 90 mg 15 27 53 60 47





from gene to clinic

107ABSTRACTS

including weight, dose, baseline PASI, worst 5-year PASI and

PASI at 3, 6, 9 and 12 months. The starting PASI calculation

method used influenced PASI 75/90 rates at 3 months using

starting PASI: only 18% achieved PASI 90 vs. 26% using worst

5-year PASI. At 3 and 6 months all groups achieved higher

PASI 75/90 when the worst 5-year PASI was used vs. starting

PASI. The dose of ustekinumab used also influenced outcomes;

only 11% of patients receiving 45-mg doses achieved PASI 90

at 3 months vs. 24% receiving 90 mg. We noted a discrep-

ancy in outcomes using different measures; 18% of patients

reached PASI 90 at 3 months, but 45% achieved PASI ≤ 3.

Response differences were also seen between groups: group 3

(80.1–100 kg, 90-mg dose) achieved higher rates of PASI ≤ 3

at 3 and 6 months than the other groups (see Table) and had

greater achievement of PASI 75/90 at 3 and 6 months. A

dose-related difference in response was also seen with 90 mg,

with patients achieving higher PASI 90 rates at 3 months,

24% vs. 11% for 45 mg, and this difference appeared to les-

sen over time with 12-month PASI 90 rates being similar:

22% vs. 26%. In conclusion, variation in the starting PASI cal-

culation methodology can lead to differences in treatment out-

come reporting, and using absolute PASI in addition to PASI

75/90 can lead to greater transparency of reported results.

Although these data lack numbers for statistical significance

the findings may warrant further investigation from larger

datasets such as BADBIR.

P072Role of keratin 24 in human epidermalkeratinocytesM. Min,1 X.-B. Chen,1 P. Wang,1 L. Landeck,2

J.-Q. Chen,1 W. Li,1 S. Cai,1 M. Zheng1 and X.-Y. Man11Dermatology Department, Second Affiliated Hospital, School of Medicine,

Zhejiang University, Hangzhou, China and 2Ernst von Bergmann General

Hospital, Teaching Hospital of Charit�e, Humboldt University, Potsdam,

GermanyThe keratins are the typical intermediate filament proteins of

epithelia, showing an outstanding degree of molecular diver-

sity. As part of the epithelial cytoskeleton, keratins are impor-

tant for the mechanical stability and integrity of epithelial cells

and tissues. Moreover, recent studies have pointed to newly

recognized roles of certain keratins in apoptosis, cell growth,

tissue polarity, wound response and tissue remodelling. The

skin maintains its barrier function through tight regulation of

the proliferation and differentiation of keratinocytes, the pri-

mary cellular component of the epidermis. Previous studies

have shown that keratin abnormalities are associated with a

variety of skin diseases, including proliferative skin diseases

and hereditary skin diseases. In psoriasis, this differentiation

process is dysregulated, and keratinocytes exhibit hyperprolif-

eration and aberrant differentiation, which are two key hall-

marks of psoriatic lesions. Keratin 24 (K24) is a new kind of

keratin gene, which encodes a novel keratin protein. K24

bears high similarity to the type I keratins and displays a

unique expression profile. K24 is reported to be highly

expressed in keratinocytes, placenta, colon and spleen.

However, the function of K24 within the skin are still

unknown. The purpose of this study was to explore the

expression pattern and biological function of K24 in epidermal

keratinocytes, by which to lay the foundation for the study of

association between K24 and psoriasis. Skin biopsies were

taken from age-matched healthy volunteers and untreated

patients with psoriasis. Total RNA and protein were extracted

from the cultured primary epidermal keratinocytes. The mRNA

and protein levels of K24 were determined by quantitative

reverse-transcriptase polymerase chain reaction (qRT-PCR) and

Western blot, respectively. We further explored the expression

and location in the epidermis of skin specimens and normal

keratinocytes by immunofluorescence staining. To investigate

the role of K24 in keratinocyte differentiation, we character-

ized the expression of K24 on subcultured keratinocytes and

calcium-inducible differentiation. To determine the role of

K24 in keratinocytes further, K24 was overexpressed in pri-

mary keratinocytes by infection with lentivirus, which was

constructed with the K24 gene. The efficiency of overexpres-

sion of K24 in normal human epidermal keratinocytes was

confirmed by qRT-PCR and Western blot. Subsequently, the

effects of K24 overexpression on proliferation, differentiation,

apoptosis, cell cycle, senescence and migration were explored

by Western blot and functional analyses. In our study, the

protein level of K24 in normal keratinocytes was found to be

higher than that in psoriatic keratinocytes. Next we investi-

gated the localization of K24 within the epidermis and possi-

ble functions. K24 was found to be modestly overexpressed in

senescent keratinocytes and was mainly restricted to the upper

stratum spinosum of the epidermis. The protein was required

for terminal differentiation upon CaCl2-induced differentia-

tion. In vitro results showed that increased K24 in keratinocytes

dramatically changed the differentiation of primary ker-

atinocytes. It also inhibited cell survival by G1/S phase cell-

cycle arrest and induced senescence, autophagy and apoptosis

of keratinocytes. In addition, K24 activated the protein kinase

Cd signal pathway, involved in cellular survival. In summary,

K24 may be suggested as a potential differentiation marker

and antiproliferative factor in the epidermis.

P073Deletion of PCSK9 can suppress psoriasis-likeinflammation in an animal modelM. Chen,1 R. Yuan,2 C. Luan,1,2 X. Chen,2

J.M. Osland,2 S.J. Gerber,2 M. Dodds2 and Y. Hu11Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing,

China and 2Southern Illinois University School of Medicine, Springfield, IL,

U.S.A.Psoriasis is a systemic inflammatory disease associated with

metabolic disorders, including high levels of low-density

lipoprotein (LDL). Proprotein convertase subtilisin/kexin 9

(PCSK9), promoting the degradation of LDL receptors and

increasing the plasma LDL concentration, is also involved in

inflammation. This study aimed to examine the role of PCSK9

in psoriasis and to investigate the potential of topically apply-

ing small interfering (si)RNA targeting Pcsk9 as a new psoriasis



treatment. We investigated the imiquimod-induced psoriatic

reactions in Pcsk9 knockout and Pcsk9 siRNA-treated mice,

and also used cultured human keratinocytes to investigate the

role of PCSK9 on regulating cell proliferation and apoptosis.

We found that suppressing Pcsk9 can decrease the inflamma-

tory reaction induced by imiquimod treatment and inhibit

hyperproliferation of keratinocytes. The underlying mecha-

nisms may operate by suppressing the expression of nuclear

factor-jB and its downstream inflammatory cytokines, includ-

ing interleukin (IL)-17, IL-22 and IL-23. We also found that

suppressing PCSK9 can significantly suppress proliferation and

induce apoptosis of human keratinocytes. Taken together, our

findings indicate that PCSK9 plays an important role in psoria-

sis, and may be a novel therapeutic target.

P074Correlation between Dermatology Life QualityIndex and Psoriasis Area and Severity Index inpatients with psoriasis treated with ustekinumabJ.H. Hesselvig, A. Egeberg, N.D. Loft, C. Zachariae,K. Kofoed and L. SkovDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital,

University of Copenhagen, Hellerup, DenmarkBiological treatment is often reserved for patients with moder-

ate-to-severe psoriasis, where initiation and evaluation of the

effect is based on the clinical evaluation and on the patient’s

quality of life. In the initial phase of the treatment period a

strong correlation between Psoriasis Area and Severity Index

(PASI) and Dermatology Life Quality Index (DLQI) has been

shown. However, long-term correlation between PASI and

DLQI for patients treated with ustekinumab has not been

investigated in a real-life setting. In this register-based study

of patients with moderate-to-severe psoriasis, we investigated

the correlation between PASI and DLQI after 4 and

12 months. All patients with psoriasis treated with ustek-

inumab (n = 120) at our department from April 2009 to

March 2017 were included. A correlation analysis between the

change in PASI and DLQI and the individual questions in DLQI

were performed using Spearman’s rank correlation coefficient.

We observed a reduction in median PASI from baseline to

month 4 and a subsequent slight reduction until month 12,

with a similar pattern for DLQI. The correlation analysis

showed a moderate association between relative reduction in

PASI and DLQI with correlation values of 0.57 (P < 0.001)

for baseline to 4 months and 0.45 (P < 0.001) for baseline to

12 months. For the individual questions in DLQI the greatest

association was observed for questions on ‘symptoms and feel-

ings’. This was mainly attributed to improvement in the

symptoms (e.g. pain and pruritus) questions, with correlation

values close to those observed between PASI and overall DLQI:

0.52 (P < 0.001) for baseline to 4 months and 0.48

(P < 0.001) for baseline to12 months. The questions regard-

ing daily activities and treatment were only weakly associated

with improvements in psoriasis severity. The results suggest

objective improvements in severity of psoriasis to be weakly

to moderately associated with improvements in quality of life

in patients with psoriasis treated with ustekinumab. This study

was supported by an unrestricted grant from Janssen-Cilag.

P075Safety, efficacy and drug survival of biologics andbiosimilars for moderate-to-severe plaque psoriasisA. Egeberg,1 M.B. Ottosen,1 R. Gniadecki,2

S. Broesby-Olsen,3 T. Dam,4 L.E. Bryld,5

M.K. Rasmussen6 and L. Skov11Department of Dermatology and Allergy, Herlev and Gentofte Hospital,

Hellerup, Denmark; 2Department of Dermatology, Bispebjerg Hospital,

Copenhagen, Denmark; 3Department of Dermatology and Allergy Centre,

Odense University Hospital, Odense, Denmark; 4Skin Clinic, Nykøbing

Falster, Denmark; 5Department of Dermatology, Roskilde Hospital, Roskilde,

Denmark and 6Department of Dermatology, Aarhus University Hospital,

Aarhus, DenmarkReal-life data on newer biologics and biosimilar agents for

moderate-to-severe psoriasis are lacking. Our objective was to

examine the safety, efficacy and time to discontinuation (drug

survival) of biologics (adalimumab, etanercept, infliximab,

secukinumab and ustekinumab) and to compare the origina-

tors with biosimilars (i.e. Enbrel with Benepali, and Remicade

with Remsima). The DERMBIO registry contains data on all

Danish patients with moderate-to-severe plaque psoriasis trea-

ted with biologics. We examined patients treated between 1

January 2007 and 31 March 2017. We used Kaplan–Meier

survival curves and Cox regression to examine drug survival

patterns. There were a total of 3495 treatment series (2161

patients) including 1332 with adalimumab, 579 with etaner-

cept (621 when stratified by originator/biosimilar; 566 with

originator etanercept and 55 with biosimilar etanercept), 333

with infliximab (356 when stratified by originator/biosimilar;

266 with originator infliximab and 90 with biosimilar inflix-

imab), 1055 with ustekinumab and 196 with secukinumab.

Secukinumab had the highest number of responders with

100% improvement in Psoriasis Area and Severity Index (PASI

100) within the first 52 weeks, but also the lowest drug sur-

vival among all biologics. Ustekinumab had the highest drug

survival overall (ustekinumab > adalimumab > infliximab >etanercept > secukinumab). Long-term efficacy (PASI 75, 90

and 100, and absolute PASI ≤ 5, 3 and 1) was highest for

ustekinumab and adalimumab. There were no significant dif-

ferences in discontinuation risk between the originator and

biosimilar versions of infliximab or etanercept. During the first

24 weeks of therapy (including the induction dose), 3.5%,

39.0%, 22.7%, 0.0% and 20.0%, of patients were treated with

a higher dose of adalimumab, etanercept, infliximab, secuk-

inumab and ustekinumab, respectively, than the European

Medicines Agency (EMA) label dose. During maintenance

therapy (weeks 25–52), the EMA label dose was exceeded in

0.9%, 35.1%, 56.7%, 0.0% and 46.2% of patients, respec-

tively. When dose escalation was included in the models,

ustekinumab still had the highest drug survival of all biolog-

ics, followed by adalimumab. Adverse events (predominantly

infections) were most frequent for secukinumab and showed

an increased (albeit low) incidence of cardiovascular events





from gene to clinic

109ABSTRACTS

compared with the other agents. In conclusion, ustekinumab

was associated with the highest drug survival, and secuk-

inumab with the lowest. Switching from originator to biosim-

ilar had no significant impact on drug survival, and the safety

profiles were comparable. Adverse events occurred most fre-

quently with secukinumab. Future studies are warranted to

assess the long-term safety of novel biologics for psoriasis.

P076Predictive factors of pruritus among patients withpsoriasisC. Ebongo, S. Mansouri and B. HassamDermatology Department of Ibn Sina Hospital, Rabat, MoroccoPsoriasis is an inflammatory disease with cutaneous and articu-

lar tropism. It was previously considered not to be prurigi-

nous, but it is now well established that pruritus is a major

sign that can seriously alter the quality of life of these patients.

However, data regarding the prevalence of pruritus in psoria-

sis and its characteristics remain insufficient. The aim of our

study was to identify the predictive factors of pruritus in pso-

riasis. We conducted a retrospective cross-sectional study. All

patients with psoriasis who were hospitalized in our unit

between January 2007 and December 2016 were included. In

total 59 files were exploited. The average age was 42.8 years

and the sex ratio was 1.5: 1 men to women. Sixty-one percent

were married and 51% were unemployed. Regarding comor-

bidities we found one diabetic patient, eight with hyperten-

sion, six with obesity, three with dyslipidaemia, three

alcoholics, 10 who used tobacco and seven followed for

depression or anxiety. Psoriasis vulgaris was the predominant

form (71%), followed by erythroderma (15%), pustular

(10%) and the inverted form (3%). The mean cutaneous sur-

face area involved was estimated to be 43% and the mean Pso-

riasis Area and Severity Index score was 20.6. Pruritus was

found in 59% of patients and was severe in 37%. The analyti-

cal study found that the erythrodermic (P = 0.048) and pustu-

lar (0.038) forms, cutaneous surface area > 70% (P = 0.04)

and PASI > 15 (P = 0.01) were significantly associated with

the presence of pruritus. In contrast, obese patients were less

likely to have pruritus (P = 0.03). More and more publica-

tions are focusing on pruritus in psoriasis and its characteris-

tics. Aggravating factors have been reported such as stress,

cold and dry climates, skin xerosis, physical exercise and lack

of sleep. Pruritus also significantly alters the quality of life of

these patients while perpetuating the lesions by the Koebner

phenomenon. Indeed, the PASI score of patients with psoriasis

with pruritus is higher than that of patients without pruritus,

suggesting that pruritus should be considered as an additional

factor of severity in psoriasis. However, studies attempting to

compare the clinical characteristics of patients with psoriasis

and the presence of pruritus are rare. Management of patients

with psoriasis must integrate the management of pruritus

because it is a major sign responsible for the sustainability of

the lesions and also affects the quality of life of patients.

P077Education of patients with psoriasisC. Ebongo, S. Mai, M. Meziane and B. HassamDermatology Department of Ibn Sina Hospital, Rabat, MoroccoPsoriasis is a chronic inflammatory disease primarily affecting

the skin and joints. It is a multifactorial disease that affects

about 1–3% of the general population. Psychological repercus-

sions and impairment of life quality are important. The suc-

cess of the treatment requires the active participation of

patients. Therapeutic education of the patient aims to help

them acquire the skills necessary to manage their life with a

chronic illness. The aim of our study was therefore to assess

the impact of therapeutic education on patients with psoriasis.

We carried out a prospective 3-month study involving around

30 patients followed in our unit for psoriasis. The same ques-

tionnaire was used before and 1 month after the therapeutic

education in order to appreciate its contribution. The ques-

tionnaire included three main items with four to five ques-

tions each. In total 23 patients were included, 15 men and

eight women, with an average age of 27.8 � 3.2 years. Half

(51%) had a school level below high school and 75% earned

< €300 per month. Concerning questions related to the trans-

mission of the disease and its symptoms, before education

one-third of the patients had a score of correct answers

> 50% vs. four-fifths after education. In terms of associated

diseases and comorbidities, only one-sixth had a score > 50%,

vs. 100% after education. Regarding the treatment modalities

available and their follow-up, only three in 10 patients had a

score of correct answers > 50% before the education, vs. eight

in 10 after the education. There are diseases where therapeutic

education has been validated and is fully part of the manage-

ment of patients, such as diabetes, in which it has improved

metabolic control of the disease, improved quality of life and

reduced complications. Indeed, a better understanding of their

pathology seems to help patients to take an active part in their

care. In dermatology, therapeutic education has already proved

its worth in patients with atopic dermatitis. It would therefore

probably be beneficial to patients with psoriasis, especially that

considering that it has a chronic pathology with a strong psy-

chological impact. Therapeutic education remains an indis-

pensable tool in the management of patients with chronic

disease. However, the limitations of our study lie in the short

duration of study and our small sample. The establishment of

a specialized and multidisciplinary consultation for better care

should be considered.

P078Psychiatric comorbidity, psychotropic medicationprescribing and suicidality in patients withpsoriasis: a population-based cohort studyR. Parisi,1 R.T. Webb,2 C.E. Kleyn,3,4 M.J. Carr,2

N. Kapur,2 C.E.M. Griffiths3,4 and D.M. Ashcroft1,4,51Centre for Pharmacoepidemiology and Drug Safety, University of Manchester,

Manchester Academic Health Science Centre, Manchester, U.K.; 2Centre for

Mental Health and Safety, University of Manchester, Manchester Academic

Health Science Centre, Manchester, U.K.; 3Dermatology Centre, Salford Royal



NHS Foundation Trust, University of Manchester, Manchester Academic

Health Science Centre, Manchester, U.K.; 4NIHR Manchester Biomedical

Research Centre, Faculty of Biology, Medicine and Health, The University of

Manchester, Manchester Academic Health Science Centre, Manchester, U.K.

and 5NIHR Greater Manchester Patient Safety Translational Research Centre,

University of Manchester, Manchester Academic Health Science Centre,

Manchester, U.K.The psychological burden in people affected by psoriasis may

lead to elevated risks of suicide and nonfatal self-harm. This

study aimed to investigate psychiatric comorbidity, psy-

chotropic medication prescribing and suicidality in people

with psoriasis. Patients with a first diagnosis of psoriasis

between 1998 and 2014 were identified from the Clinical

Practice Research Datalink linked to Hospital Episode Statistics

and the Office for National Statistics mortality records in Eng-

land. For each patient with psoriasis, up to 20 comparison

patients were matched by age, sex, general practice and index

date. A stratified Cox proportional hazard model was used to

estimate the risk of suicide and nonfatal self-harm in people

with psoriasis. The multivariate model was adjusted for

socioeconomic status. Statistical models with interactions were

tested; these included an interaction between psoriasis and

age, sex or socioeconomic status. The cohort included 56 961

patients with psoriasis and 876 919 comparison patients. At

baseline, people with psoriasis had a higher prevalence of

depression (18.8% vs. 16.4%), anxiety (17.8% vs. 15.9%) and

bipolar disorder (0.64% vs. 0.51%) and were more often pre-

scribed psychotropic medications (54.5% vs. 49.1%). The

baseline prevalence of schizophrenia, eating disorder and per-

sonality disorder were similarly distributed in the psoriasis

and comparison cohorts (0.90% vs. 0.89%, 0.83% vs. 0.80%

and 0.56% vs. 0.55%, respectively). During a median follow-

up of 4.4 years (interquartile range 6.1), 35 and 679 suicide

events occurred in the psoriasis and comparison groups,

respectively, and, after exclusion of patients with a history of

self-harm, 592 and 6914 first self-harm events occurred in the

psoriasis and comparison cohorts, respectively. When taking

into account socioeconomic status, the risk of suicide was sig-

nificantly lower among patients with psoriasis [hazard ratio

(HR) 0.59, 95% confidence interval (CI) 0.41–0.85], and

there was no significant difference in risk of nonfatal self-

harm (HR 1.06, 95% CI 0.97–1.17). After testing for interac-

tions, the risk of suicide significantly differed according to age

(P = 0.02). The HR was 0.38 (95% CI 0.21–0.66) for patientsdiagnosed with psoriasis at ≥ 40 years, but there was no sig-

nificant difference in risk for those diagnosed at age

< 40 years. People with psoriasis have a greater prevalence of

depression and anxiety and are more likely to be prescribed

psychotropic medication than the general population. Never-

theless, having psoriasis is not associated with an elevated risk

of either suicide or nonfatal self-harm.

P079Dithranol in psoriasis: keratinocyte–neutrophilcross-talk as the early targetT.H. Benezeder,1 C. Painsi,2 G. Mayer,1

U. Schmidbauer,1 K. Hammer,2 B. Lange-Asschenfeld2 and P. Wolf1

1Department of Dermatology, Medical University of Graz, Graz, Austria and2Department of Dermatology, State Hospital Klagenfurt, Klagenfurt, AustriaDithranol is one of the most potent topical treatments for pso-

riasis, leading to fast Psoriasis Area and Severity Index (PASI)

reduction. Application of dithranol causes inflammation, but

its mechanisms of action have remained largely unclear until

now. The aim of this study was to investigate the therapeutic

mechanisms of dithranol treatment in plaque-type psoriasis.

Biopsy samples from 15 patients with psoriasis (mean baseline

PASI score 13.6 � 10.6) were taken before (day 0), during

(day 4 at maximum inflammation) and at the end of treat-

ment (week 2–3), and at the follow-up after dithranol therapy

(week 6–7). Dithranol treatment had reduced PASI in these

patients by a mean of 57% (range 42–74%) at week 2–3 and

by 59% (range 3–81%) in the follow-up. Gene expression in

the skin samples was evaluated by using Affymetrix Human

Gene 2.0 Arrays, and differentially expressed genes were iden-

tified based on fold changes (> 2.0) and t-tests (P < 0.05).

Gene expression analysis revealed significant upregulation with

a more normalized pattern of genes involved in establishment

of the skin barrier, epithelial homeostasis and keratinization in

lesional skin after 4 days of dithranol treatment compared

with baseline. Furthermore, antimicrobial peptides and

chemoattractants for neutrophils (e.g. CXCL8) were signifi-

cantly downregulated compared with lesional skin before

treatment. At the end of treatment the expression of these

genes decreased further and other genes involved in neu-

trophil-mediated inflammatory responses were also signifi-

cantly downregulated. With delay, proinflammatory cytokines

(interleukins IL-1b, IL-17, IL-22 and IL-36) significantly

decreased only at the end of treatment (week 2–3). Notably,genes involved in T-cell activation were not differentially

expressed during dithranol treatment. Consistently, a signifi-

cant decrease in dermal CD3, CD4, FoxP3 and CD8 cell counts

(as quantified by immunohistochemistry) was only seen at the

follow-up visit but not during dithranol treatment. Together

our results suggest that keratinocytes and their cross-talk with

neutrophils (and not cells of the acquired immune system)

are the primary targets of dithranol. (T.B. and C.P. equally

contributed to this work.)

P080Effectiveness and safety of off-label secukinumabdosing regimens for the treatment of moderate-to-severe plaque psoriasis in adult patients: aretrospective multicentre studyM. Phung,1 J.R. Georgakopoulos,2 A. Ighani3 andJ. Yeung4,51Department of Pharmacology and Toxicology, University of Toronto,

Toronto, ON, Canada; 2Schulich School of Medicine and Dentistry, Western





from gene to clinic

111ABSTRACTS

University, London, ON, Canada; 3Faculty of Medicine, University of

Toronto, Toronto, ON, Canada; 4Division of Dermatology, Faculty of

Medicine, University of Toronto, Toronto, ON, Canada and 5Probity Medical

Inc., Waterloo, ON, CanadaSecukinumab is a fully human IgG1k anti-interleukin (IL)-17A

monoclonal antibody used for the treatment of moderate-to-

severe plaque psoriasis in adult patients. It is widely accepted

that the proinflammatory cytokine IL-17A plays a central role

in the pathophysiology of this skin disease. Although secuk-

inumab 300 mg every 4 weeks has shown to be highly effec-

tive and safe, select patients in clinical practice display only a

partial response with this approved maintenance dosing regi-

men. Similarly, select patients achieve effective outcomes

immediately following the prescribed weekly loading doses;

however, they display minor disease relapse during the

interim period between injections. Clinicians may consider

using off-label dosing regimens to treat these patients due to

their unsatisfactory response to the approved regimen. Secuk-

inumab dose optimization involves shortening the dosing

interval of maintenance therapy. To our knowledge, no study

has evaluated the effectiveness and safety of these alternative

dosing regimens. Therefore, we aimed to evaluate off-label

secukinumab dosing regimens to inform real-world clinical

practice. We performed a multicentre, retrospective chart

review of patients aged ≥ 18 years treated with an off-label

secukinumab updosing regimen for moderate-to-severe plaque

psoriasis. Effectiveness [≥ 75% improvement in Psoriasis Area

and Severity Index (PASI 75) or Physician’s Global Assessment

(PGA) of 0 or 1] and safety (adverse events) were assessed at

baseline, prior to and after dose optimization. Of the six

patients who met inclusion criteria, four (67%) achieved and

two (33%) did not achieve PASI 75 or PGA 0/1 after

12 weeks of secukinumab treatment with the approved main-

tenance dosing regimen. These patients then elected to dose

optimize, where four (67%) patients had their dosing frequency

increased to 300 mg every 3 weeks, and two (33%) had theirs

increased to 300 mg every 2 weeks. After 12 weeks of treat-

ment with optimized dosing, all six (100%) patients achieved

PASI 75 from baseline or PGA 0/1. Overall, these patients expe-

rienced a significant clinical improvement after 12 weeks of

treatment with optimized dosing. No adverse events were

reported following dose optimization. These preliminary find-

ings suggest that increasing the dosing frequency of secuk-

inumab is safe and effective, benefitting patients with an

unsatisfactory clinical response to the approved dosing regimen.

In summary, dose optimization with secukinumab may be ben-

eficial in some patients with moderate-to-severe plaque psoriasis

and should be considered by clinicians in clinical practice.

P081Comorbidities in patients with psoriasis accordingto Charlson Comorbidity Index: 6 years ofexperience in Bogot�a, ColombiaC. Cortes, E. Pe~naranda, D. Chaparro, L. Pe~na andE. RoaHospital Universitario de la Samaritana, Bogot�a, Colombia

The survival of patients with psoriasis is modified by the

inflammatory component of this disease, especially when it is

associated with comorbidities. This which forces us to

improve promotion and prevention strategies in this group of

patients. Few studies have been carried out using a validated

comorbidity index that allows the practitioner to infer predic-

tive mortality information. The Charlson Comorbidity Index is

a score that includes 17 systemic diseases, used to predict the

5-year mortality of patients based on their different comor-

bidities. The University Hospital La Samaritana is a reference

centre for the state of Cundinamarca (Colombia), which has

socioeconomic conditions that differ from those of popula-

tions in which similar studies have been carried out. We do

not have studies in Colombia that allow us to know which are

the most frequent comorbidities in patients with psoriasis, or

the relationship of these comorbidities with the severity of

psoriasis. Our conclusions were as follows. The most prevalent

comorbidities in adult patients with psoriasis treated at the

University Hospital La Samaritana are dyslipidaemia (32%),

hypertension (26.1%) and obesity (23.8%). We did not find

a statistically significant association between the presence of

comorbidities and the clinical severity of psoriasis in this

group of patients. Cardiovascular and metabolic comorbidi-

ties are present in this group of patients regardless of clini-

cal severity. Charlson Comorbidity Index does not include

the most prevalent comorbidities in patients with psoriasis

(dyslipidaemia, hypertension and obesity), so we do not

consider it a good indicator of disease burden in this group

of patients. Studies that evaluate the association between

clinical severity of psoriasis and mortality are required.

Screening strategies should be implemented for all patients

diagnosed with psoriasis treated at the University Hospital

La Samaritana for the main comorbidities, regardless of

clinical severity.

P082Relationship between age of onset, male-to-femaleratio and family history of Japanese patients withpsoriasis: comparison with other East AsiancountriesB. Bayaraa and S. ImafukuFukuoka University, Fukuoka, JapanPsoriasis develops in patients of any age; however, the peak

age of onset differs among countries and ethnic groups. The

histogram of age of onset in Japanese patients with psoriasis is

bimodal, but the reason is yet unclear. To clarify the relation-

ship of age at onset, sex and family history of psoriasis in

Japanese patients with psoriasis, data from the Fukuoka

University Psoriasis Registry (FUPR) were analysed. Patients

who visited the Department of Dermatology, Fukuoka

University Hospital from 1998 to 2016 and were diagnosed

as having psoriasis were all registered at FUPR. Patients aged

0–79 years were extracted and analysed. To find out further

the characteristics of Japanese patients, the results were com-

pared with previously published similar data from other East

Asian countries. A total of 1089 patients were found in FUPR.



The male-to-female ratio was 2.04 : 1. Two peaks of distribu-

tion in age of onset were seen, with the first peak in the 30s

for men and the 20s in women, and the second peak in the

50s for both sexes. Family history of psoriasis was seen in

6.4% in total; however, female patients had a much higher

rate (9.0%) compared with men (5.2%, P = 0.018). Further-

more, when stratified by age of onset, female patients with

onset < 30 years had a much higher rate (15.4%) than

women with onset > 30 years (5.6%, P = 0.0032). When

these data were compared with those from South Korea and

China, the onset age in both countries had a single peak,

which was located at a younger age than in Japan. Japanese

patents showed higher male predominance than those in

South Korea and China. South Korean and Chinese patients

had much more familial psoriasis (26% and 31%, respectively)

than Japanese. Age of onset of psoriasis in Japanese patients

was characteristically higher in both men and women than in

other Asian countries, with fewer cases of familial psoriasis.

Genetic background may affect these differences.

P083The journey of adult patients with psoriasistowards biologics past and present: results fromthe BioCAPTURE registryJ. van den Reek,1 M. Seyger,1 P. van L€uimig,1

R. Driessen,1 L. Schalkwijk,1 M. Berends,2 P. van deKerkhof1 and E. de Jong11Radboud University Medical Center, Department of Dermatology, Nijmegen,

the Netherlands and 2Slingeland Hospital, Doetinchem, the NetherlandsA considerable disease period, of 20 years on average, often

precedes initiation of a biological drug in patients with psoria-

sis. Little is known about this long but important period in

patients’ lives. An evaluation of this ‘journey’, and shifts

thereof in recent years, can reveal important insight and

opportunities for physicians, healthcare decision makers and

pharmaceutical manufacturers. We therefore aimed to describe

important patient and treatment characteristics until the start

of biological treatment in a cohort of patients with severe pso-

riasis. Moreover, we aimed to assess shifts of the ‘journey’ in

early (2005–2009) vs. established (2010–2015) biologics pre-scription periods. We performed an explorative, retrospective

study analysing the treatment characteristics of the period

from psoriasis diagnosis until first biologic. Data were col-

lected from the BioCAPTURE registry, presented with descrip-

tive statistics and visualized in bar charts. The journeys of

2005–2009 and 2010–2015 were compared with statistical

tests (e.g. v2-test and Mann–Whitney U-test) to identify

important shifts. Most patients received three different conven-

tional antipsoriatic systemic therapies before initiation of the

biologic. Methotrexate, ciclosporin and acitretin were most

frequently used. We noticed a small trend towards a shorter

‘journey’ with only two conventional systemic agents instead

of three before initiating a biologic in later years (2010–2015vs. 2005–2009). Ciclosporin, intensive topical treatment

(dithranol) and ultraviolet therapy have lost popularity in

recent years. The number of patients with hospital admissions

and day care admissions during the ‘journey’ significantly

decreased in patients starting a biologic in later years (2010–2015 vs. 2005–2009). We also noticed a significant decrease

in the rate of (day care) admissions in the 2 years before vs. the

2 first years during biological treatment. For instance, in the

period before starting a biologic, 17.7 admissions (day care

and hospital) per 100 follow-up years were seen vs. 8.6

admissions per 100 follow-up years in the first years of bio-

logical therapy (P < 0.001). To conclude, the journey of

patients with psoriasis towards a biologic is often extensive in

duration and in use of multiple conventional antipsoriatic

treatments. Discussion should continue on how to improve

this ‘journey’, as it could be a burdensome period with nega-

tive influence on patients’ lives and societal impact. The costs

of biologics, the safety profile of conventional systemic and

biologics, and the decrease in admissions during biologics

should be taken into account here. We think that especially

young and recently diagnosed patients could benefit from

optimization of their ‘journey’ towards biologics.

P084Skin mast cells: critical drivers of psoriasis?M.J. Barron, C.E.M. Griffiths and S. Bulfone-PausDivision of Musculoskeletal & Dermatological Sciences, School of Biological

Sciences, Faculty of Biology, Medicine and Health, University of Manchester,

Manchester, U.K.The aim of this study was to investigate the role of mast cells

(MCs) in the pathogenesis of psoriasis. We used immunohis-

tochemistry and metachromatic staining to evaluate MC distri-

bution and function in biopsies of psoriasis lesional (PP),

psoriasis nonlesional (PN) and healthy (NN) skin. Addition-

ally, we performed RNA sequencing analysis using cultured

MCs and those isolated from PP and PN skin. In PP skin there

was a twofold increase in MC density and a threefold increase

in the incidence of degranulation compared with PN and NN

skin. CD8� T cells in PP skin showed a 10-fold increased den-

sity, while macrophage density was increased fivefold. Finally,

nerve fibre and vascular density in PP skin were unchanged

and slightly raised, respectively, compared with PN and NN.

The relationship of MCs with CD8+ T lymphocytes and

macrophages showed strong spatial association in all skin

types analysed. However, in PP skin, MCs and nerve fibres

showed increased spatial association while MCs lost their

strong spatial association with the vasculature. In PP skin there

was a threefold increase in interleukin (IL)-17+ cells and a

parallel increase in IL-17+ MCs. We have isolated MCs from

PP and PN using flow cytometry and performed RNA sequenc-

ing analysis to delineate the gene expression of MCs in psoria-

sis. Our preliminary results show a dramatically increased

expression of genes involved in immune cell chemoattraction

in PP mast cells compared with those from PN, for example

CXCL1 (3.8), CXCL2 (2.3), CXCL3 (3.6), IL8 (2.8), CCL2 (1.8)

and CCL4 (3.0); the numbers in brackets are log2 fold

changes. This increased expression of chemoattractant genes

was also particularly pronounced in MCs from PP when





from gene to clinic

113ABSTRACTS

compared with quiescent MCs derived from peripheral blood,

including CXCL1 (5.1), CXCL2 (7.7), CXCL3 (4.8), IL8 (7.3),

CCL2 (2.9) and CCL4 (3.3); the numbers in brackets are log2fold changes. Our results show an increased prevalence of

MCs in PP skin in parallel with both CD8+ T cells and macro-

phages, two cell types that strongly associate with MCs. Fur-

thermore, the PP MCs population appears to traffic from the

vasculature to interact with dermal nerve fibres. Pruritus is a

common and distressing feature of psoriasis and the increased

proximity of MCs to nerve fibres in PP skin may be correlated

with this. The strong representation of proinflammatory,

chemoattractant genes and IL-17 expression in PP skin MCs is

consistent with this cell population being pivotal in driving

the inflammatory process in psoriasis.

P085Secukinumab demonstrates high sustained efficacyand a favourable safety profile through 5 years oftreatment in moderate-to-severe psoriasisR. Bissonnette,1 T. Luger,2 D. Thac�i,3 D. Toth,4,5

A. Lacombe,6 S. Xia,7 R. Mazur,6 P. Manmath,6

C. Pascal,6 M. Milutinovic6 and C. Leonardi81Innovaderm Research, Montreal, QC, Canada; 2University of M€unster,

M€unster, Germany; 3University Hospital Schleswig-Holstein, L€ubeck,

Germany; 4Probity Medical Research Windsor, Windsor, ON, Canada;5XLR8 Medical Research, Windsor, ON, Canada; 6Novartis Pharma AG,

Basel, Switzerland; 7Beijing Novartis Pharma Co. Ltd, Beijing, China and8Saint Louis University Health Science Center, St Louis, MO, U.S.A.Psoriasis is a chronic immune-mediated skin disease usually

requiring long-term management. Secukinumab, a fully

human monoclonal antibody that neutralizes interleukin (IL)-

17A, has been shown to have significant efficacy in the treat-

ment of moderate-to-severe psoriasis and psoriatic arthritis,

demonstrating sustained and long-lasting high levels of effi-

cacy with a favourable safety profile. This is the first phase III

study of an IL-17A inhibitor presenting long-term sustainabil-

ity and safety for up to 5 years of continuous treatment at the

approved dose. In the core SCULPTURE study, patients who

were Psoriasis Area and Severity Index (PASI) 75 responders

(≥ 75% improvement from baseline) at week 12 continued

receiving subcutaneous secukinumab 300 mg every 4 weeks

until year 1 (n = 168 at week 52). Patients subsequently

entered the extension phase and continued the same double-

blinded treatment regimen to year 3, and were thereafter

unblinded to year 5 (n = 126 at week 260), which was the

end of the study. Here we report final PASI 75/90/100, abso-

lute body surface area (BSA) ≤ 1/≤ 2/≤ 3, absolute

PASI ≤ 1/≤ 2/≤ 3 responses, Dermatology Life Quality Index

(DLQI) 0/1 response and safety and tolerability to year 5. Effi-

cacy data are reported as observed, and safety events are anal-

ysed per year. The mean baseline PASI and BSA were

23.5 � 8.8 and 33.1% � 18.9, respectively. PASI 75/90/100

responses at year 1 (88.9%, 68.5% and 43.8%, respectively)

were well sustained to year 5 (88.5%, 66.4% and 41%). The

average improvement in mean PASI was approximately 90%

compared with baseline through 5 years. Absolute PASI ≤ 1/

≤ 2/≤ 3 responses were sustained from year 1 (58.6%, 67.9%

and 74.1%, respectively) to year 5 (53.3%, 66.4% and

75.4%). Similarly, absolute BSA ≤ 1/≤ 2/≤ 3 responses at

year 1 (60.5%, 73.5% and 77.2%, respectively) sustained to

year 5 (62.3%, 71.3% and 78.7%). Two-thirds of patients

reported no impact of skin disease on their lives over 5 years

of treatment; DLQI 0/1 responses were 72.7% at year 1 and

65.5% at year 5. The safety profile of secukinumab remained

favourable, with no cumulative or unexpected safety concerns

identified. The most common adverse events included

nasopharyngitis, upper respiratory tract infection and head-

ache, consistent with those reported in the core study and pre-

vious phase III studies. The most frequent reasons for

discontinuation in the extension study were patient or guar-

dian decision (13, 7.7%), adverse event (10, 6%) and lack of

efficacy (seven, 4.2%). Secukinumab 300 mg treatment sus-

tained high levels of skin clearance, and improved quality of

life, through 5 years in patients with moderate-to-severe pso-

riasis. The favourable safety established in a large phase III

programme was maintained to 5 years. This investigation was

sponsored by Novartis Pharma AG, Basel, Switzerland.

P086Infliximab is associated with an increased risk ofserious infection in patients with psoriasis: resultsfrom the British Association of DermatologistsBiologic Interventions Register (BADBIR)Z. Yiu,1 C. Smith,2 D. Ashcroft,3 M. Lunt,4

S. Walton,5 R. Murphy,6 N. Reynolds,7,8

A. Ormerod,9 C.E.M Griffiths1 and R.B. Warren1

1Dermatology Centre, Salford Royal NHS Foundation Trust, The University

of Manchester, Manchester Academic Health Science Centre, NIHR

Manchester Biomedical Research Centre, Manchester, U.K.; 2St John’s

Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust,

London, U.K.; 3Centre for Pharmacoepidemiology and Drug Safety, School of

Health Sciences, The University of Manchester, Manchester, U.K.; 4Arthritis

Research U.K. Epidemiology Unit, The University of Manchester, Manchester,

U.K.; 5Department of Dermatology, Castle Hill Hospital, Hull, U.K.;6Sheffield University Teaching Hospitals and Sheffield Children’s Hospitals,

Sheffield, U.K.; 7Dermatological Sciences, Institute of Cellular Medicine,

Medical School, Newcastle University Newcastle upon Tyne, U.K.;8Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals

NHS Foundation Trust, Newcastle upon Tyne, U.K. and 9Division of Applied

Medicine, University of Aberdeen, Foresterhill, Aberdeen, U.K.There is concern that infliximab use for the management of

psoriasis may be associated with an increased risk of serious

infections. In the U.K., infliximab use for psoriasis is reserved

for patients with very severe disease [Psoriasis Area and Sever-

ity Index (PASI) ≥ 20; Dermatology Life Quality Index

(DLQI) > 18] compared with other biologics (PASI ≥ 10;

DLQI > 10). Thus, infliximab differs from other biologics in

that it is dosed intravenously and to a more severe population.

To account for this, we investigated the risk of serious infec-

tions associated with infliximab separately from the other bio-

logical therapies in patients with chronic plaque psoriasis

using a large prospective, U.K. and Republic of Ireland-based



pharmacovigilance registry (British Association of Dermatolo-

gists Biologic Interventions Register, BADBIR) reflecting real-

life clinical practice. The infliximab-treated cohort was com-

pared with a biologic-naive cohort who had received systemic

therapy, inclusive of exposure to methotrexate, ciclosporin,

acitretin, fumaric acid esters, psoralen–ultraviolet A or hydrox-

ycarbamide. Serious infections were those associated with hos-

pitalization, the use of intravenous antimicrobial therapy and/

or death. Propensity score inverse probability treatment-

weighted Cox proportional hazards models, adjusted for a pri-

ori identified potential confounders (including disease sever-

ity), were used to compare the risk of serious infection.

Missing data were accounted for using multiple imputations

of 20 cycles. All analyses were undertaken using Stata v14. In

total 3843 participants were included for analysis up to Octo-

ber 2016. The total and median follow-up time for infliximab

were 941.1 and 1.5 person-years [interquartile range (IQR)

2.5 person-years], and for the nonbiologic systemic cohort

6419.2 person-years and 1.5 (IQR 1.8) person-years. Forty-

five of 422 participants in the infliximab cohort experienced a

serious infection; 91 of 3421 participants experienced a seri-

ous infection in the nonbiologic systemic cohort. The inci-

dence rates were 47.8 per 1000 person-years [95% confidence

interval (CI) 35.7–64.0] in the infliximab cohort and 14.2 per

1000 person-years (95% CI 11.5–17.4) in the nonbiologic

systemic cohort. Infliximab was associated with a significantly

increased risk of serious infection overall (adjusted hazard

ratio 1.95, 95% CI 1.01–3.75). These data show that inflix-

imab use for psoriasis is associated with an increased risk of

serious infections compared with nonbiologic systemic thera-

pies. This risk should be taken into account when considering

infliximab for the management of patients with severe

psoriasis.

P087Efficacy and tolerance assessment of an anti-itching spray in patients with psoriasisS. Virassamynaik,1 B. Chadoutaud,2 C. Eydieux,2

J. Riviere2 and M. Sayag11Naos (Laboratoire Bioderma), Lyon, France and 2ClinReal Online, Toulouse,

FrancePsoriasis is a chronic and inflammatory skin disease where

patients usually experience pruritus. This symptom can have a

huge impact on their quality of life (e.g. sleep problems, dis-

comfort in daily activities). In order to sooth pruritus, an anti-

itching spray has been developed. It combines the Skin

ReliefTM technology and enoxolone, which have a specific

action on pruritus. To demonstrate its antipruritic efficacy and

the tolerance in patients with psoriasis, an observational,

prospective, multicentre study was carried in Poland. Thirty

patients with mild-to-moderate psoriasis were included by

three dermatologists. During 21 days, the spray was applied as

often as necessary on the area affected by pruritus. Efficacy

was evaluated by the 5D-pruritus scale and a clinical assess-

ment of the skin. Impact on the quality of life (Skindex) and

tolerance were assessed as secondary end points. After 21 days

of use, a significant decrease of the 5D-pruritus scale score

(�36%) and itching sensations (�48%) were observed. The

spray relieves pruritus in 20.2 s on average and the effect

lasted ≥ 2 h in 80% of patients. The cutaneous state was sig-

nificantly improved (dryness �41%, roughness �43%,

desquamation �43%, suppleness +25% and lesion extent

�29%). The product demonstrated a positive impact on qual-

ity of life by a significant decrease of Skindex score (�37%).

The spray was well tolerated by 100% of the patients. In con-

clusion, this study demonstrated that the spray quickly calms

the itching associated with psoriasis and provided patients

with sustainable relief. The spray not only improved symp-

toms, but was shown to enhance self-image and the social life

of patients.

P088Gene expression and protein changes from bloodand skin correlate with disease improvement inpatients with psoriasis treated with PF06700841,a tyrosine kinase2/Janus kinase 1 inhibitorL. Xi,1 E. Kieras,1 M. Suarez-Farinas,2 B. Zhang,1

K. Page,1 J. Lee,1 S. Du,3 L. Fitz,1 W. Gordon,3

W. Zhang,4 J. Krueger5 and E. Peeva31Pfizer Clinical Research, Cambridge, MA, U.S.A.; 2Icahn School of Medicine

at Mount Sinai, New York, NY, U.S.A.; 3Pfizer Inflammation &

Immunology Research, Cambridge, MA, U.S.A.; 4Pfizer Global Product

Development, Cambridge, MA, U.S.A. and 5The Rockefeller University, New

York, NY, U.S.A.A biomarker analysis from a phase I clinical study was con-

ducted to identify treatment response biomarkers of gene and

protein changes in blood and skin, and disease improvement

in patients with psoriasis treated with a tyrosine kinase 2/

Janus kinase 1 inhibitor. Skin biopsies and blood samples were

collected at weeks 0, 2 and 4 from patients enrolled in a study

designed to test the safety and efficacy of PF06700841, taken

once daily at 30 mg (n = 14) or 100 mg (n = 7), compared

with placebo (n = 9) for 4 weeks. Gene expression was quan-

tified from skin biopsies using the Affymetrix Human Genome

U133 Plus 2.0 Array and from Paxgene blood samples using

next-generation sequencing-based RNA sequencing on the

Illumina platform. Proteins (n = 303) were quantified in

serum using the Olink Proseek Multiplex Inflammation and

Cardiovascular (II & III) and Immuno-Oncology panels. A lin-

ear mixed model was used to evaluate the relationship

between change from baseline in biomarker measurements

and Psoriasis Area and Severity Index score, and to identify

biomarkers that respond to treatment. Genes downstream of

interferon-c (PLK3, CBX7 and IFIH1) and interleukin (IL)-17

(PDZK1IP1, PI3, LCN2, S100A8 and S100A9) correlated with dis-

ease improvement (P < 0.05) and were significantly modu-

lated in treated patients in skin or blood. Thirteen genes

correlated with disease improvement in both blood

(P < 0.05) and in skin (false discovery rate < 0.05). Two

genes showed interesting relationships between gene expres-

sion and protein and in tissue vs. blood. A mature dendritic

cell marker, LAMP3, showed decreased gene expression in skin,





from gene to clinic

115ABSTRACTS

as well as decreased protein in serum (P < 0.05); the gene

signal was not detected in blood. Another dendritic cell mar-

ker previously shown to colocalize with lymphocytes in psori-

asis lesions, CD83, was also downregulated in skin, as was the

protein in serum (30-mg treatment, false discovery rate

< 0.1), while there was an increase in gene expression in

blood. Treatment also induced downregulation of genes asso-

ciated with IL-4 signalling in skin, whereas increased expres-

sion of these genes was observed in blood. This approach to

compare gene expression and proteins in blood and skin iden-

tified a set of biomarkers associated with disease improvement

or treatment response. Several blood-based biomarkers were

identified that correspond to changes in skin. The differences

and parallels in biomarker modulation in blood and skin pro-

vide insights into the biological mechanisms of PF06700841

inhibition in psoriasis. Further investigation of these biomark-

ers in a larger cohort is warranted. This work was funded by

Pfizer.

P089Interleukin (IL)-36c induces IL-23 production andangiogenesis in psoriasisC. Bridgewood,1 G. Fearnley,2 A. Keszegpal,2

P. Laws,3 S. Ponnambalam,2 A. Graham,1 M. Stacey2

and M. Wittmann21University of Bradford, Bradford, U.K.; 2University of Leeds, Leeds, U.K.

and 3Chapel Allerton Hospital, Leeds, U.K.The interleukin (IL)-1 family member cytokine IL-36c is rec-

ognized as a crucial mediator in the immunopathology of pso-

riasis, hallmarks of which include the activation of both

resident and infiltrating inflammatory myeloid cells, and aber-

rant angiogenesis. This research demonstrates a role for IL-36cin both myeloid activation and angiogenesis. We show that

IL-36c induces the production of psoriasis-associated cytokines

from macrophages (IL-23, tumour necrosis factor-a) and that

this response is enhanced in macrophages from patients with

psoriasis. This effect is specific for IL-36c and could not be

mimicked by other IL-1 family cytokines such as IL-1a.IL-36c was also demonstrated to induce endothelial tube for-

mation and branching, in a vascular endothelial growth

factor-A-dependent manner. Furthermore, IL-36c-stimulated

macrophages potently activated endothelial cells as illustrated

by ICAM-1(CD54) upregulation, and led to increased adher-

ence of monocytes, effects that were markedly more pro-

nounced for psoriatic macrophages. Interestingly, regardless of

stimulus, psoriasis monocytes showed increased adherence to

both the stimulated and unstimulated endothelium when com-

pared with monocytes from healthy individuals. Collectively,

these findings add to the growing evidence for IL-36c having

roles in psoriatic responses, by enhancing endothelium-direc-

ted leucocyte infiltration into the skin and strengthening the

IL-23/IL-17 pathway. Our findings also point to a cellular

response that could potentially support cardiovascular

comorbidities in psoriasis in the form of increased monocyte

adherence.

P090One-year pilot study to evaluate sequential therapywith ciclosporin and itolizumab in treatment ofchronic plaque psoriasisU. Chakravadhanula,1 B.S. Chandrashekar,2

M. Parekh,3 D.S. Krupashankar,4 H.S. Swaroop5 andD. Pawar5

1SK Health Care foundation, Hyderabad, India; 2Cutis Academy of Cutaneous

Sciences, Bangalore, India; 3Jain Hospital, Bangalore, India; 4Malligae

Hospital, Bangalore, India and 5Medical Affairs, Biocon, Bangalore, IndiaItolizumab, an anti-CD6 monoclonal antibody, acts upstream

and inhibits the formation of cytokines. However, activation

of a positive feedback loop in keratinocytes leads to a delay its

onset of action. Hence this study has been conducted to target

the positive feedback loop initiated by interleukin-17 using

ciclosporin, and to target the upstream mediator CD6 by itoli-

zumab. This combined targeting could lead to faster control

and longer remission of psoriasis. Thus our objective was to

assess the efficacy of itolizumab as a sequential therapy with

ciclosporin in the treatment of patients with moderate-to-

severe plaque psoriasis. Adult patients with psoriasis with Pso-

riasis Area and Severity Index (PASI) > 10 were administered

oral ciclosporin 3–5 mg kg�1 bodyweight for the first

15 days. After a 24-h drug-free period, itolizumab 1.6 mg

kg�1 was administered intravenously every 15 days for the

first 3 months and thereafter monthly for the next 3 months.

Change in PASI score was evaluated every month until

52 weeks from the initiation of itolizumab. Twelve patients

with moderate-to-severe psoriasis with a mean baseline PASI

of 24.4 (range 10–47.5) were recruited. They achieved a

mean PASI score of 18.9 (range 5–36.5) after 14 days of

ciclosporin. After 12 weeks of itolizumab therapy seven

(58%) patients achieved PASI 75 (≥ 75% improvement from

baseline), with mean PASI score of 5.0 (range 2.6–7), and

two (16%) achieved PASI 90 with a mean PASI score of 1.1

(range 0.6–1.6). After 24 weeks of itolizumab therapy four

(33%) patients achieved PASI 75 with a mean PASI score of

4.6 (range 3.6–6.6) and six (50%) patients achieved PASI 90

with a mean PASI score of 1.6 (range 0.4–4.6). Two patients

failed to achieve PASI 75 after 24 weeks and withdrew from

the study. Nine (75%) patients maintained PASI 75 response

at the end of 52 weeks of itolizumab therapy. Two patients

had developed infusion reactions with mild severity during

the course of the therapy. The main limitation of the study is

the absence of a control group. In conclusion, sequential

blocking of both upstream and downstream mediators by

ciclosporin and itolizumab offers encouraging efficacy with

long-term remission. However, this needs to validated with

randomized controlled studies.

P091Examining the impact of treatment by adermatologist vs. nondermatologist in psoriasiscareM. Porter,1 N. Golbari,1,2 S. Lockwood1 andA. Kimball1



1Beth Israel Deaconess Medical Center, Boston, MA, U.S.A. and 2Stony

Brook School of Medicine, Stony Brook, NY, U.S.A.Despite recent treatment advances in the care of patients with

psoriasis, almost half of patients remain untreated or under-

treated (Armstrong AW, Robertson AD, Wu J et al. Undertreat-

ment, treatment trends, and treatment dissatisfaction among

patients with psoriasis and psoriatic arthritis in the United

States: findings from the National Psoriasis Foundation sur-

veys, 2003–2011. JAMA Dermatol 2013; 149: 1180–5). We

sought to identify patient-reported differences in disease man-

agement practices and treatment satisfaction when patients

were treated by dermatologists vs. nondermatologists (primary

care providers or rheumatologists). A 36-question survey was

administered to patients with psoriasis at Massachusetts Gen-

eral Hospital (MGH) and a local National Psoriasis Foundation

conference. All responses to the survey, including assessment

of disease severity, were self-reported. Only patients at MGH

had a verified diagnosis of psoriasis. Preliminary data included

responses from 60 patients. Treatment was prescribed by a

dermatologist for 52 patients vs. by a nondermatologist for

eight. Overall 73% of patients with psoriasis treated by a der-

matologist were also first diagnosed by a dermatologist, and,

similarly, 64% treated by a nondermatologist were first diag-

nosed by a nondermatologist. When comparing patients trea-

ted by dermatologists vs. nondermatologists, those treated by

dermatologists reported having psoriasis longer (20.2 vs.

11.6 years, P = 0.06), having greater disease improvement

(50% vs. 13%, P = 0.047), having greater satisfaction with

treatment (80% vs. 50%, P = 0.06) and feeling more

informed (89% vs. 57%, P = 0.03). Only 27% of dermatolo-

gist-treated patients reported mild disease, compared with

75% of nondermatologist-treated patients. Twelve patients

reported being treated with biological agents, and all were

prescribed by dermatologists. Our study found that patients

treated by dermatologists reported greater improvements in

their disease despite having more severe disease. Only derma-

tologists prescribed biological agents to those surveyed, and

this trend was also found in a previous survey of primary care

providers where none reported prescribing systemic therapy

(Lockwood S, Porter M, Kimball A. Addressing the under-

treatment of patients with psoriasis, preliminary survey results.

In: Society for Investigative Dermatology Annual Conference. Portland,

Oregon, 2017). Improving access to dermatology or education

and training for nondermatologists about psoriasis therapy

may benefit untreated or undertreated patients with psoriasis,

particularly those with severe or refractory disease. Further

studies to design targeted interventions for nondermatologists

or the referral process should be performed. Fellowship fund-

ing for two of the authors was provided through the National

Psoriasis Foundation.

P092Ixekizumab maintains reductions in Psoriasis Areaand Severity Index through the third year oftreatment: results from the UNCOVER-3 extensionstudyP. Fern�andez-Pe~nas,1 O. Goldblum,2 L. Berggren,2

N. Burkhardt2 and L. Puig31Depatment of Dermatology, Westmead Hospital, Westmead, Australia;2Eli Lilly and Company, Indianapolis, IN, U.S.A., and 3Dermatology Service,

Hospital de la Santa Creu i Sant Pau, Barcelona, SpainFor long-term assessment of efficacy, the achievement of a

low absolute Psoriasis Area and Severity Index (PASI) may be

more relevant than relative improvement from baseline PASI.

Here we report 3-year (156-week) PASI data of patients trea-

ted with ixekizumab, a high-affinity anti-interleukin (IL)-17A

monoclonal antibody. Patients received ixekizumab according

to the recommended dose (starting dose 160 mg, then 80 mg

every 2 weeks up to and including week 12, followed by

80 mg every 4 weeks) in the UNCOVER-3 study

(NCT01646177). Only visits treated at the recommended

ixekizumab dose were considered. Data collected after the first

visit with uptitrated 2-weekly long-term dosing were excluded

before imputations were applied. Data were summarized using

two methods. Firstly, multiple imputation (MI): partial impu-

tation of nonmonotone missing data (for intermittent missing

data) using a Markov chain Monte Carlo method with the

simple imputation model, then for the monotone missing

data, a sequential regression multiple imputation with the

baseline score. Secondly, mNRI (modified nonresponder

imputation): patients who discontinued due to adverse events

or lack of efficacy/relapse were considered nonresponders and

were imputed as nonresponders. In all other cases of missing

data for this analysis, the data were imputed using the above

MI method. At week 156, 249 of 385 patients (64.7%) had a

nonmissing PASI score with the recommended dose, and 136

of 385 patients (35.3%) had a missing value and were

imputed. The relative PASI responses were (MI/mNRI) PASI

75, 91.1%/83.9%; PASI 90, 76.9%/72.2%; PASI 100, 53.9%/

51.6%. At 156 weeks, the absolute PASI values were (MI/

mNRI) PASI ≤ 5, 91.5%/84.2%; PASI ≤ 3, 83.6%/78.0%;

PASI ≤ 2, 79.1%/74.5%; PASI ≤ 1, 70.0%/66.5%. No new

safety signals were seen for ixekizumab. In conclusion, ixek-

izumab showed sustained efficacy through 3 years of treat-

ment in clearing psoriasis, while maintaining a favourable

safety profile. This study was funded by Eli Lilly and Com-

pany, Indianapolis, IN, U.S.A.

P093Starting biologic treatment sequences for plaquepsoriasis with ustekinumab or adalimumab is themost cost-effective: a cost–utility analysis basedon 10 years of Dutch real-world evidence fromBioCAPTURES. Klijn,1 J. van den Reek,2 G. van de Wetering,1

A. van der Kolk,3 E. de Jong2 and W. Kievit4





from gene to clinic

117ABSTRACTS

1Pharmerit International, Health Economics and Outcomes Research,

Rotterdam, the Netherlands; 2Department of Dermatology and 4Radboud

Institute for Health Science, Radboud UMC, Nijmegen, the Netherlands and3Janssen-Cilag BV, Breda, the NetherlandsTreatment with biologics, such as etanercept, adalimumab or

ustekinumab, may be indicated for patients with moderate-to-

severe plaque psoriasis. Switching of biologics is common, but

it is unclear which biologic is most effective to initiate a

sequence of biologics. Comparative evidence on (cost)-effec-

tiveness of different biologics is limited. Given that biologics are

associated with high treatment costs, appropriate use of these

drugs is necessary. We aimed to evaluate the cost-effectiveness

of different biological treatment sequences for psoriasis based

on real-world evidence. A sequence model was developed to

evaluate the costs and health effects of different consecutive

lines of biological treatments based on the three most com-

monly prescribed biologics: adalimumab, etanercept and ustek-

inumab (for example adalimumab-etanercept-ustekinumab vs.

etanercept-ustekinumab-adalimumab) over a 10-year time hori-

zon. The model was populated with data from the Dutch Bio-

CAPTURE registry and scientific literature. The model estimated

10-year treatment costs and the total quality-adjusted life years

(QALYs) for each possible treatment sequence. Uncertainty was

addressed by both probabilistic and scenario analyses. We esti-

mated that sequences starting with etanercept would be the

most expensive, with 10-year costs from €147 499 to

€ 148 442; it was also the least effective with an average cumu-

lative health effect of 7.79 QALYs. A sequence starting with

ustekinumab followed by adalimumab would be the least

expensive, with 10-year costs of €141 962, while the cumula-

tive health effect is estimated to be 8.02 QALYs. A sequence

starting with adalimumab followed by ustekinumab was mar-

ginally more effective with 8.03 QALYs, but was also slightly

more expensive, with 10-year costs of €143 661. When inter-

preting these results, it should be taken into account that the

credible intervals were partly overlapping. We conclude from

these findings that the order in which biologics are used influ-

ences the cost-effectiveness of treatment in terms of both costs

and health effects. Initiation of a biological treatment sequence

for psoriasis may best be done with adalimumab or ustek-

inumab; etanercept seems less optimal from a health-economic

perspective. As the sequence order of biologics influences both

costs and health effects of psoriasis treatment, adopting a long-

term perspective at the start of treatment is important.

P09452-Week results from IXORA-S: a randomizedhead-to-head trial of ixekizumab and ustekinumabin patients with moderate-to-severe plaquepsoriasisC. Paul,1 P. van de Kerkhof,2 Y. Dutronc,3

C. Henneges,3 M. Dossenbach,3 K. Hollister3 andK. Reich4,5

1Dermatology, CHU, Paul Sabatier University, Toulouse, France; 2Department

of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, the

Netherlands; 3Eli Lilly and Company, Indianapolis, IN, U.S.A.,

4Dermatologikum Hamburg, Hamburg, Germany and 5SCIderm Research

Institute, Hamburg, GermanyIxekizumab is a high-affinity monoclonal antibody that selec-

tively targets interleukin-17A. It has demonstrated superior effi-

cacy to ustekinumab through Week 24 in IXORA-S

(NCT02561806) (Reich K, Pinter A, Lacour JP et al. Comparison

of ixekizumab with ustekinumab in moderate-to-severe psoria-

sis: 24-week results from IXORA-S, a phase III study. Br J Dermatol

2017; in press; https://doi.org/10.1111/bjd.15666). Here we

present the 1-year comparative efficacy and safety data. Patients

were randomized (1 : 1) to ixekizumab (n = 136) or ustek-

inumab (n = 166), dosed per their approved labels. Categorical

data were analysed using logistic regression including terms for

treatment, weight and geographical region. Nonresponder

imputation was used to account for missing data. The incidence

of adverse events (AE) between groups was compared using

Fisher’s exact test. This study was funded by Eli Lilly and Com-

pany, U.S.A. At week 52, the majority of efficacy response rates

were significantly higher for ixekizumab than for ustekinumab.

Treatment-emergent AEs (TEAEs), serious AEs and infection

rates were comparable between the two treatment groups; no

deaths occurred. Nasopharyngitis was the most common TEAE

and infection type. Significantly more injection-site reactions

occurred in the ixekizumab group. The results from IXORA-S

demonstrate the continued superior efficacy of ixekizumab over

ustekinumab at week 52. The safety profiles of both treatment

groups were in line with published reports [Reich et al.; Papp

KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustek-

inumab, a human interleukin-12/23 monoclonal antibody, in

patients with psoriasis: 52-week results from a randomised,

double-blind, placebo-controlled trial (PHOENIX 2). Lancet

2008; 371: 1675–84].

Ustekinumab,n = 166

Ixekizumab,n = 136 P-value

Response, n (%)

PASI 75 126 (75.9) 120 (88.2) 0.006PASI 90 98 (59.0) 104 (76.5) 0.003

PASI 100 59 (35.5) 71 (52.2) 0.014sPGA (0–1) 108 (65.1) 110 (82.1) 0.002

DLQI (0–1) 94 (56.6) 97 (71.3) 0.014Itch NRS ≥ 4-point

improvement

101 (74.3) 88 (80.0) 0.24

Safety, n (%)

TEAE 139 (83.7) 117 (86.7) 0.52Nasopharyngitis 63 (38.0) 45 (33.3) –Headache 21 (12.7) 15 (11.1) –Arthralgia 14 (8.4) 11 (8.1) –Serious AE 6 (3.6) 9 (6.7) 0.29Infections/infestations 107 (64.5) 83 (61.5) 0.63

Nasopharyngitis 63 (38.0) 45 (33.3) –Influenza 6 (3.6) 8 (5.9) –Bronchitis 9 (5.4) 3 (2.2) –Injection-site reactions 2 (1.2) 22 (16.3) < 0.001

DLQI, Dermatology Life Quality Index; NRS, Numerical Rating

Scale; PASI, Psoriasis Area and Severity Index; sPGA, Static Physi-

cian Global Assessment.



P095The genotype of susceptibility genes in psoriasispredicting the response and hepatotoxicity tomethotrexate treatmentJ. Xu,1 X. Zhang1,2 and K. Yan11Huashan Hospital, Shanghai, China and 2Anhui Medical University, Anhui,

ChinaMethotrexate is an efficacious and cost-effective treatment as a

first-line agent for moderate-to-severe psoriasis. However, it is

limited in its use by unpredictable efficacy and toxicity. This

study was designed to test the hypothesis that susceptibility

genetic variations are associated with the efficacy and hepato-

toxicity of methotrexate. DNA was collected from 90 patients

with psoriasis who had been treated with methotrexate in a

prospective cohort. Phenotypic data on efficacy and hepatotox-

icity were available. Eighteen single-nucleotide polymorphisms

in 15 susceptibility genes were selected from our previous

reported susceptibility loci of psoriasis. The AG genotype in

CLE3D (rs4112788) and the TT genotype in TNIP1

(rs10036748) are associated with good response to

methotrexate therapy in patients with psoriasis; the latter gene

was also associated with hepatotoxicity. The TT genotype in

TNIP1 (rs10036748) and the AA genotype in ERAP1 (rs27043)

are related to the development of arthritis in patients with

psoriasis. These data indicate that the genotype of susceptibil-

ity genes may predict the efficacy and hepatotoxicity of

methotrexate treatment in psoriasis.

P096Evaluation of the efficacy of granulocyte andmonocyte adsorption apheresis on skinmanifestation and joint symptoms of patients withpustulotic arthro-osteitisH. Kawakami,1,2 N. Abe,1 Y. Matsumoto,1 H. Hirano,1

R. Tsuboi1 and Y. Okubo1

1Tokyo Medical University, Tokyo, Japan and 2Ageo Central General

Hospital, Saitama, JapanPustulotic arthro-osteitis (PAO), occasionally complicated with

palmoplantar pustulosis (PPP), affects patients’ activities of

daily living. Granulocyte and monocyte adsorption apheresis

(GMA) selectively removes activated granulocytes and mono-

cytes by means of extracorporeal circulation. Although the

efficacy of GMA in the treatment of generalized pustular psori-

asis has been proven, very few reports have assessed its effi-

cacy in the treatment of PPP and PAO. We treated 10 patients

with PAO including five with PPP skin manifestations with a

weekly GMA session over 5 weeks. Skin manifestations were

assessed using the PPP Area and Severity Index (PPPASI), and

joint symptoms were assessed using a visual analogue scale of

joint pain, tender joint count, swollen joint count and high-

sensitivity C-reactive protein immediately before, immediately

after, and at the 3-month follow-up of the five GMA sessions.

Two of five patients with PPP symptoms achieved > 50%

improvement in their PPPASI score (remarkably improved).

However, in two patients, deterioration of the skin symptoms

was noted, in one of whom the skin manifestations remained

unchanged at the 3-month follow-up. In five of the 10

patients with PAO, the joint symptoms were assessed as better

than ‘improved’ at the 3-month follow-up. No deterioration

was noted at the 3-month follow-up. In three patients, reduc-

tion or cessation of medication for arthralgia was possible

after GMA therapy. Based on these findings, we conclude that

GMA is a valid therapeutic option for patients with PAO.

P097Multicomponent biomarkers: a novel method foraccurate diagnosis of psoriasisF. L€attekivi,1 E. Reimann,1 M. Keermann,2,3

K. Abram,2,3 S. K~oks,1,4 K. Kingo2,3 and A. Fazeli1,51Department of Pathophysiology and 2Department of Dermatology, University

of Tartu, Tartu, Estonia; 3Clinic of Dermatology, Tartu University Hospital,

Tartu, Estonia; 4Department of Reproductive Biology, Estonian University of

Life Sciences, Tartu, Estonia and 5Academic Unit of Reproductive and

Developmental Medicine, Department of Oncology and Metabolism, The

Medical School, University of Sheffield, Sheffield, U.K.The accurate diagnosis of psoriasis has remained a challenge,

as no disease-specific biomarkers have yet been identified.

Currently, the diagnosis of chronic inflammatory diseases

relies mainly on the assessment of visible symptoms or the

histological features of the biopsy. This approach is heavily

reliant on the experience of the clinician and, therefore, may

lead to misdiagnosis as there are numerous different chronic

inflammatory skin diseases that may present similar clinical

features. Hence, the need for diagnostic biomarkers is clear.

Although different investigations have reported the discovery

of potential psoriasis biomarkers, still no accurate and reliable

biomarker is available. Rather than searching for a single valid

biomarker, we propose that applying a multicomponent bio-

marker-based approach would result in a higher degree of

success and translation into clinical practice. An extensive

review of published studies to identify the most relevant pso-

riasis-specific biomarker candidates was conducted. This led us

to conclude that the expression levels of specific genes in the

skin hold the most promise as discriminatory biomarkers,

resulting in the selection of five genes, the expression levels of

which have been demonstrated to be exclusive for psoriasis

vulgaris. We first conducted a preliminary validation study

applying support vector machine-based classification and prin-

ciple component analysis on the skin-derived expression data

of 12 patients with psoriasis vulgaris and 12 healthy controls,

previously produced in our departments. We then confirmed

that the expression levels of the five genes in psoriatic lesions

indeed present a unique pattern. Encouraged by these results,

we continued to develop a quantitative polymerase chain reac-

tion panel to allow the accurate measurement of expression

levels for the five genes to be used in the studies to follow.

Although we have yet to confirm these results in the context

of other chronic inflammatory skin diseases, the results of pre-

viously published studies regarding these five genes are

promising. Therefore, we are in the process of collecting addi-

tional skin samples from patients with chronic inflammatory

disease (including different papulosquamous disorders and





from gene to clinic

119ABSTRACTS

atopic dermatitis) to validate the discriminatory power of our

panel. These results may further be translated to viable clinical

diagnostic tests in the near future. This work was supported

by the ERA Chair for Translational Genomics and Personalized

Medicine at the University of Tartu.

P098Genome-wide DNA methylation profiling identifiesdifferential methylation in uninvolved psoriaticepidermisD. Verma, A.-K. Ekman, C.B. Eding and C. Enerb€ackIngrid Asp Psoriasis Center, Link€oping University, Link€oping, SwedenPsoriasis is a chronic inflammatory skin disease with both local

and systemic components. Genome-wide approaches have

identified more than 60 psoriasis-susceptibility loci, but genes

are estimated to explain only one-third of the heritability in

psoriasis, suggesting additional, yet unidentified, sources of

heritability. Epigenetic modifications have been linked to pso-

riasis, and altered DNA methylation patterns in psoriatic vs.

healthy skin have been reported in whole-skin biopsies. In this

study, focusing on epigenetic modifications in psoriatic unin-

volved skin, we compared the lesional and nonlesional epider-

mis from patients with psoriasis with epidermis from healthy

controls. We performed an exhaustive genome-wide DNA

methylation profiling using reduced representation bisulfite

sequencing, which interrogates the methylation status of

around 3–4 million CpG sites. More than 2000 strongly dif-

ferentially methylated sites (DMSs) were identified, and a

striking overrepresentation of the Wnt and cadherin pathways

among the DMSs was found. In particular, we observed a

strong differential methylation in several psoriasis candidate

genes. A substantial number of DMSs present in uninvolved

vs. healthy epidermis suggests the presence of a prepsoriatic

epigenetic signature. Our exploratory study represents a start-

ing point for identifying biomarkers for psoriasis-prone skin

before disease onset.

P099Gene expression changes induced by individualinterleukin (IL)-17 family cytokines signallingthrough IL-17RAD.A. Ewald, P. Lovato, T. Skak-Nielsen andH. NorsgaardLEO Pharma, Ballerup, DenmarkThe interleukin (IL)-23/IL-17 immune axis is of key impor-

tance for driving skin inflammation in psoriasis. However, the

importance of IL-17 family cytokines in psoriasis other than

IL-17A has not been fully elucidated. In this study, we investi-

gated the global transcriptional profile induced by IL-17 fam-

ily cytokine signalling through IL-17RA. For this purpose,

full-thickness punch biopsies of healthy skin were cultured in

the presence of individual IL-17 family cytokines for 24 h.

Gene expression profiling was carried out on whole-transcript

arrays (Affymetrix Human Gene 2.1 ST). We contrasted these

profiles with those of untreated controls, and compared the

resulting differential expression profiles with those of psoriatic

lesional vs. nonlesional skin. Ranked-list comparison and com-

parative gene set enrichment analysis indicated that the

IL-17A-, IL-17A/F- and IL-17F-induced expression profiles

most closely resemble the expression signature of psoriatic

skin. In comparison, the IL-17C-induced expression profile

overlaps to a lower degree with the psoriasis signature,

whereas the IL-17E-induced expression profile shows negligi-

ble overlap with the psoriasis signature. The global expression

findings were further confirmed by quantitative reverse-tran-

scriptase polymerase chain reaction on selected genes. The

expression of DEFB4A was strongly upregulated by IL-17A,

IL-17A/F and IL-17F, although with differences in potency.

IL-17C also increased the expression of DEFB4A but to a mark-

edly lower level, whereas IL-17E had no effect on the expres-

sion of DEFB4A. A comparable pattern was seen for other

IL-17-responsive genes, such as S100A7 and LCN2. In line with

these results, gene expression of DEFB4A in human primary

keratinocyte cultures was induced by IL-17A, IL-17F and

IL-17C in synergy with tumour necrosis factor-a to a high,

intermediate and low level, respectively. The induction of

DEFB4A by IL-17A, IL-17F and IL-17C was downregulated by

IL-17RA antagonism. The above findings indicate that IL-17A,

IL-17A/F and IL-17F, and to a lesser extent IL-17C, can all

induce gene expression changes similar to those observed in

psoriatic skin lesions. This suggests that combined inhibition

of IL-17 family cytokines, for example by targeting of the

IL-17RA receptor, could be a favoured mechanism for normal-

ization of the psoriasis-associated gene expression signature.

P100Validity of self-reported psoriasis in a Danish birthcohortC. Blegvad,1,2 T.E.T. Nielsen,1,2 C. Zachariae,1

A.-M.N. Andersen2 and L. Skov1

1Department of Dermatology and Allergy, Herlev and Gentofte Hospital,

University of Copenhagen, Copenhagen, Denmark and 2Section of Social

Medicine, Department of Public Health, University of Copenhagen,

Copenhagen, DenmarkSelf-reported disease is an inherent part of many register-based

studies. The validity of a self-reported diagnosis is therefore of

great importance. The aim of this study was to examine the

validity of self-reported psoriasis. As part of a larger clinical

study on children with psoriasis, we invited mothers and their

children for clinical examination. The mother–child pairs were

identified using a large birth cohort, the Danish National Birth

Cohort (DNBC), consisting of approximately 100 000 mothers

included via a telephone interview during pregnancy from

1997 to 2002. The mothers and their children have since been

followed up with internet-based questionnaires at child age 7

and 11 years. The mothers reported both their own psoriasis

status, at time of inclusion during pregnancy, and the child’s

psoriasis status, when the child was 11 years old. The ques-

tion to the mothers during pregnancy regarding their own

psoriasis status was whether they had ever been diagnosed

with psoriasis by a physician. The question to the mothers at

child age 11 years regarding the psoriasis status of their child



was whether the child had ever had an eruption of the skin

disease psoriasis. We invited the mother–child pairs in three

groups based on the psoriasis status given in the DNBC: ‘child

with psoriasis’, ‘mother with psoriasis’ and ‘healthy control’.

Maternal psoriasis status was confirmed on the basis of a his-

tory of physician-diagnosed psoriasis, on clinical appearance

where possible, and in case of doubt by consultation with a

senior dermatologist. Confirmation of psoriasis in the child

was done by means of a thorough clinical examination of the

skin in combination with anamnestic criteria. In case of doubt

a senior dermatologist was consulted. Fifty-eight children with

a positive DNBC psoriasis status were examined, and of these

only 28 (48%) could be confirmed as having psoriasis with

onset before the 11-year questionnaire. In regards to the

mothers, we could confirm the DNBC psoriasis status in 97

out of 120 (80.8%) from the ‘mother with psoriasis’ group.

Our study shows that the validity of self-reported psoriasis in

an adult female population is high in comparison with the

validity of the psoriasis status reported in their 11-year-old

children. The main reason for this is probably the use of

physician-diagnosed vs. self-diagnosed psoriasis. Furthermore,

psoriasis can be difficult to diagnose in children due to mild

symptoms.

P101Intentional and unintentional medicationnonadherence in psoriasis: the role of patients’medication beliefs and habit strengthR. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft,L. Cordingley and on behalf of the PSORT studygroup and BADBIRUniversity of Manchester and Manchester Academic Health Science Centre,

Manchester, U.K.Medication nonadherence is a missed opportunity for thera-

peutic benefit. Patients’ beliefs about their medication are key

drivers of nonadherence; however, there is a lack of high-

quality data on nonadherence to systemic therapies used for

psoriasis outside of clinical trials. As part of the Psoriasis Strati-

fication to Optimise Relevant Therapy (PSORT) consortium,

we assessed ‘real-world’ levels of self-reported nonadherence

to conventional and biological systemic therapies and evalu-

ated psychological and biomedical factors associated with non-

adherence using multivariable analyses. Cross-sectional data

from 811 patients with moderate-to-severe psoriasis using a

conventional systemic (35.3%) or biological therapy (64.7%)

were collected from 35 dermatology centres across England.

All patients were enrolled in the British Association of Derma-

tologists Biologic Interventions Register (BADBIR). A question-

naire assessed patients’ illness and medication beliefs (Revised

Illness Perception Questionnaire and Beliefs about Medicines

Questionnaire), psychological distress (Hospital Anxiety and

Depression Scale), the strength of the patient’s routine or habit

for using their medication (Self-Reported Habit Index) and

medication adherence (Medication Adherence Report Scale,

MARS), with a score ≤ 38 out of 40 on the MARS indicating

nonadherence. Patients’ biomedical data were obtained from

the registry. A significant proportion of patients using conven-

tional systemic (methotrexate, ciclosporin, acitretin, fumaric

acid esters) or biological therapies (etanercept, adalimumab)

were classified as nonadherent (22.4%); 12% were intention-

ally nonadherent, such as deliberately altering the dose, timing

or frequency of their therapy, and were 10.9% unintentionally

nonadherent, such as forgetting to use their therapy. Only

7.3% of patients using ustekinumab were classified as non-

adherent. Patients using a conventional systemic were signifi-

cantly more likely to be classified as nonadherent compared

with those using etanercept or adalimumab (29.2% vs. 16.4%;

P ≤ 0.001). After accounting for relevant variables, patients

who expressed the strongest concerns about their systemic

therapy and medicines in general were significantly more

likely to be classified as intentionally nonadherent (odds ratio

2.27, 95% confidence interval 1.16–4.47). Patients who

reported weaker routine or habit for using their therapy were

significantly more likely to be classified as unintentionally

nonadherent (odds ratio 0.92, 95% confidence interval 0.89–0.96). Medication nonadherence needs to be assessed when

determining factors influencing treatment response. Medica-

tion beliefs and habit strength are important modifiable targets

for strategies to improve adherence and clinical outcomes in

the management of psoriasis. C.E.M.G. is a National Institute

for Health Research Senior Investigator. PSORT is funded by

the Medical Research Council, grant MR/1011808/1.

P102Prognostic effect of psoriasis and psoriatic arthritisin patients with suspected coronary artery diseaseassessed by cardiac computed tomography:a multicentre cohort studyK.F. Hjuler,1 S. Winther,2 M. Bøttcher2 andL. Iversen1

1Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark

and 2Department of Cardiology, Hospital Unit West, Herning, DenmarkEpidemiological population-based studies assessing cardiovas-

cular disease (CVD) in patients with psoriasis have been based

on registries containing diagnoses coded by clinicians. How-

ever, detailed clinical information is still needed about the

correlation between disease activity in both psoriasis and pso-

riatic arthritis (PsA) and the risk of CVD. This study was based

on data from a subregistry to the Western Denmark Heart

Registry (WDHR), the Western Denmark Cardiac Computed

Tomography Registry. This clinical registry contains informa-

tion on approximately 60 000 cardiac computed tomography

(CT) scans from 2008 to 2015 and has shown both high

completeness and high internal validity. Furthermore, WDHR

contains data on clinical information seldom available in reg-

istries. All nine sites collaborating in WDHR register patients

consecutively in a catchment area of 3.3 million inhabitants

(55% of the Danish population). The purpose of this study

was to acquire detailed clinical information on the association

between both psoriasis and PsA and coronary artery disease,

coronary interventions and major adverse cardiac events, in a

large population-based cohort. This cohort study included





from gene to clinic

121ABSTRACTS

39 125 patients [48.2% men; median age 57.6 years,

interquartile range (IQR) 49.1–65.6] with symptoms of coro-

nary artery disease (CAD), who underwent cardiac CT, of

whom 1325 (3.5%) were identified as having psoriasis

(45.6% men; median age 59.9 years, IQR 52.0–66.7) and

309 (0.8%) as having PsA (44.7% men; median age

58.4 years, IQR 52.2–63.1). The median duration of follow-

up was 2.8 years (IQR 1.3–4.5). The maximum duration of

follow-up was 8.4 years. The proportion of patients with vs.

without psoriasis with coronary artery calcium (CAC) score

> 0 was 47.5% [95% confidence interval (CI) 44.9–50.2] vs.

40.7% (95% CI 40.2–41.2). More patients with than without

psoriasis had luminal abnormalities (30.4% vs. 26.7%; differ-

ence between proportions 3.73%, 95% CI 1.24–6.23). The

proportion of patients with PsA vs. patients without psoriasis

with CAC score > 0 was 42.4% vs. 40.9%. The proportion of

patients with PsA with luminal abnormalities was not different

from that in patients without psoriasis. Myocardial infarction

occurred in 1.3% of patients with psoriasis and 2.6% of

patients with PsA vs. 0.9% of patients without psoriasis. The

composite end point occurred in 8.4% of patients with psoria-

sis and 10.0% of patients with PsA vs. 7.4% of patients with-

out. Compared with patients without psoriasis, a higher

relative risk of the composite end point was observed for

patients with psoriasis [hazard ratio (HR) 1.16; 95% CI 0.95–1.41] and PsA (HR 1.41, 95% CI 0.98–2.02). However, in

psoriasis, the risk was reduced after adjustment for CVD risk

factors (HR 1.05, 95% CI 0.86–1.27), whereas it remained

significantly increased in patients with PsA (HR 1.50, 95% CI

1.04–2.14). In conclusion, this study based on unique data

from a large population-based cardiac CT registry showed that

the extent of CAD was increased in patients with psoriasis,

whereas the risk of CVD events was not increased. Despite

only slightly increased CAD, the risk of CVD events was

increased in patients with PsA.

P103Safety of guselkumab in patients with plaquepsoriasis through 2 years: a pooled analysis fromVOYAGE 1 and VOYAGE 2K. Reich,1 K. Papp,2 A.W. Armstrong,3 Y. Wasfi,4

G. Jiang,4 Y.-K. Shen,4 B. Randazzo,4 M. Song4 andA.B. Kimball51Dermatologikum Hamburg and SCIderm Research Institute, Hamburg,

Germany; 2K. Papp Clinical Research and Probity Medical Research,

Waterloo, ON, Canada; 3University of Southern California, Los Angeles, CA,

U.S.A.; 4Janssen Research & Development, LLC, Spring House, PA, U.S.A.

and 5Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical

Center, Inc., Boston, MA, U.S.A.We evaluated the safety of guselkumab in patients with mod-

erate-to-severe psoriasis from the VOYAGE 1 and 2 studies

through 2 years. In the phase III, randomized, double-blind,

placebo/active comparator-controlled VOYAGE 1 (n = 837)

and VOYAGE 2 (n = 992) trials, patients (age ≥ 18 years) had

plaque psoriasis for ≥ 6 months, Investigator’s Global Assess-

ment scores ≥ 3, Psoriasis Area and Severity Index scores ≥

12, ≥ 10% body surface area involvement, and were candi-

dates for systemic or phototherapy. Patients were randomized

to guselkumab, placebo or adalimumab at baseline. Placebo

patients crossed over to receive guselkumab at week 16 and

adalimumab patients crossed over to receive guselkumab

either at week 52 (VOYAGE 1) or week 28 or beyond (VOY-

AGE 2). Here we present safety data (event rates adjusted for

follow-up: per 100 patient-years) through 2 years for patients

who were initially randomized to guselkumab and those who

were randomized to placebo and crossed over to guselkumab

at week 16. Among the guselkumab-treated patients, overall

safety event rates were comparable through year 1 and cumu-

latively through year 2. Additionally, safety data from patients

on adalimumab who crossed over to guselkumab were consis-

tent with the overall guselkumab safety data, with no addi-

tional safety signals identified. In conclusion, the safety profile

of guselkumab through up to 2 years of continuous treatment

was consistent with that observed through 1 year.

Guselkumab 100 mg Year 1 Year 2

Patients 1221 1221

Total patient-yearsof follow-up

974 2084

Common AEsper 100

patient-yearsof follow-up

259.42 210.41

Nasopharyngitis 32.84 26.78Upper respiratory

tract infection

17.24 14.11

Bronchitis 3.49 2.69AEs leading to

discontinuation

2.36 1.82

Serious AEs 6.05 6.29

Infections 97.69 81.74Infections requiring

treatment

26.48 23.76

Serious infections 1.03 1.06

Malignancies(excluding NMSC)a

0.31(0.06–0.90)

0.38(0.17–0.76)

Non-melanomaskin cancer

(NMSC)a

0.62(0.23–1.34)

0.39(0.17–0.76)

MACEa 0.41

(0.11–1.05)0.38

(0.17–0.76)

Values are reported as event rates per 100 patient-years. AE,

adverse event; MACE, major adverse cardiac event; NMSC, non-

melanoma skin cancer. aWith 95% confidence interval.

P104Additional efficacy benefit of continuousixekizumab every-2-week dosing among patientswith psoriasis who do not respond by week 12K. Papp,1,2 M. Gooderham,3 P. Polzer,4 L. Zhang4

and M. Augustin5

1K. Papp Clinical Research, Waterloo, ON, Canada; 2Probity Medical

Research, Waterloo, ON, Canada; 3Queen’s University, SKiN Centre for



Dermatology, Peterborough, ON, Canada; 4Eli Lilly and Company,

Indianapolis, IN, U.S.A. and 5Institute for Health Services Research in

Dermatology and Nursing, University Medical Center, Hamburg, GermanyIxekizumab, an interleukin (IL)-17A antagonist, previously

demonstrated long-term efficacy and safety in pivotal phase III

trials. However, these trials did not contain long-term contin-

uous every-2-week (Q2W) dosing, which may benefit those

patients who do not respond by week 12. Thus, we evaluated

efficacy through 52 weeks in static Physician’s Global Assess-

ment (sPGA) 0/1 responders and nonresponders in IXORA-P,

which included a continuous Q2W dosing group through

week 52. In IXORA-P (NCT02513550), a phase III, multicen-

tre, randomized, double-blinded trial, patients with moderate-

to-severe plaque psoriasis were randomized at a 2 : 1 : 1 ratio

to three dosing regimens of 80-mg ixekizumab: continuous

Q2W (n = 611), continuous Q4W (n = 310) or Q4W/Q2W

dose adjustment per protocol (n = 306), each with a 160-mg

starting dose. Dose adjustment from Q4W to Q2W was deter-

mined by predefined criteria to which investigators were

blinded (72 patients, 23.5%, dose adjusted). Data from

patients who were nonresponders at week 12 (defined by

sPGA > 1) and received ixekizumab Q2W/Q4W (n = 65) or

continuous Q4W (n = 225) in the three UNCOVER trials

(NCT01474512, NCT01597245 and NCT01646177) were

integrated through 52 weeks. Missing data were imputed

using nonresponder imputation. The Bucher indirect compar-

ison method was used to compare continuous Q2W (IXORA-

P) and current label dose of Q2W/Q4W (UNCOVER trials),

with a common comparator of continuous Q4W. In IXORA-P,

81%, 67% and 73% of patients in the Q2W, Q4W and Q4W/

Q2W dose adjustment groups, respectively, were sPGA 0/1

responders at week 12. Among the responders at week 12,

85%, 86% and 82% of patients in the Q2W, Q4W and Q4W/

Q2W dose adjustment groups, respectively, maintained sPGA

0/1 response at week 52. Among the nonresponders at week

12, 64%, 42% and 52% of patients in the Q2W, Q4W and

Q4W/Q2W dose adjustment groups, respectively, achieved

sPGA 0/1 response at week 52, while the response for the

Q4W group (42%) was comparable with that in the inte-

grated UNCOVER Q4W/Q4W group (44%). The sPGA 0/1

response at week 52 was significantly higher in the IXORA-P

continuous Q2W group (64%) than in the integrated

UNCOVER Q2W/Q4W group (36%, P < 0.001) with Bucher

indirect comparison. There were no clinically relevant differ-

ences in regard to safety between responders and nonrespon-

ders. Overall, sPGA 0/1 responses at week 52 were similar

across all dosing groups among patients who were responders

at week 12. Among patients who were nonresponders at week

12, sPGA 0/1 responses were higher at week 52 in patients

treated continuously with Q2W compared with patients trea-

ted continuously with Q4W in the IXORA-P trial, and also

when compared indirectly with week 12 nonresponders trea-

ted with Q2W/Q4W (label dose) in the integrated UNCOVER

trials.

P105Absolute Psoriasis Area and Severity Indeximprovement through 2 years of guselkumabtreatment in the VOYAGE 1 trial of patients withplaque psoriasisK. Papp,1 C.E.M. Griffiths,2 A.B. Kimball,3 S. Li,4

Y.-K. Shen,4 Y. Wasfi4 and A. Blauvelt5

1K. Papp Clinical Research and Probity Medical Research, Waterloo, ON,

Canada; 2Dermatology Centre, Salford Royal Hospital, University of

Manchester, Manchester Academic Health Science Centre, Manchester, U.K.;3Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA,

U.S.A.; 4Janssen Research & Development, LLC, Spring House, PA, U.S.A.

and 5Oregon Medical Research Center, Portland, OR, U.S.A.The study objective was to assess efficacy responses based on

absolute Psoriasis Area and Severity Index (PASI) improvement

through 2 years of guselkumab treatment in the VOYAGE 1

trial. VOYAGE1 is a phase III, randomized, double-blinded,

placebo–active comparator-controlled trial. Eligible patients

(age ≥ 18 years) had moderate-to-severe plaque psoriasis for

≥ 6 months, an Investigator’s Global Assessment score ≥ 3,

PASI score ≥ 12, ≥ 10% body surface area involvement, and

were candidates for systemic or phototherapy. In total 837

Skin response by PASI category through week 100, %

Placebo Guselkumab Adalimumab

Randomized

patients

174 329 334

PASI score

categoriesWeek 16 174 329 334

0 0.6 37.4; P < 0.001c 17.1; P < 0.001c

≤ 1 5.2 60.5; P < 0.001c 35.3; P < 0.001c

≤ 3 6.9 84.8; P < 0.001c 64.4; P < 0.001c

Week 24a 165 329 334

0 22.4 44.4 24.9; P < 0.001d

≤ 1 35.2 69.9 41.9; P < 0.001d

≤ 3 67.9 90.9 68.3; P < 0.001d

Wk48a 165 329 334

0 50.3 47.4 23.4; P < 0.001d

≤ 1 66.7 72 43.4; P < 0.001d

≤ 3 94.5 89.4 66.2; P < 0.001d

Week 76a,b 159 300 276

0 53.5 56.3 53.3

≤ 1 75.5 71 70.3≤ 3 95.6 89.7 93.5

Week 100a,b 158 290 2750 55.1 49 51.6

≤ 1 70.9 68.6 69.8≤ 3 93 88.3 88.7

Through week 48, nonresponder imputation was used for missing

data after applying treatment failure rules. From weeks 52 to 100,

observed data were used after applying treatment failure rules.aAmong placebo-randomized patients, includes only those crossing

over to guselkumab after week 16. bAmong adalimumab-rando-

mized patients, includes only those crossing over to guselkumab

after week 52. cP-values based on comparisons vs. placebo. dP-

values based on guselkumab vs. adalimumab.





from gene to clinic

123ABSTRACTS

patients were randomized (2 : 1 : 2) to guselkumab 100 mg

at weeks 0, 4 and 12, then every 8 weeks; placebo at weeks

0, 4 and 12 followed by guselkumab 100 mg at weeks 16

and 20 then every 8 weeks; or adalimumab 80 mg at week 0,

40 mg at week 1 then 40 mg every 2 weeks through weeks

47, followed by guselkumab at week 52 then every 8 weeks.

Efficacy data through week 100 based on absolute PASI

response thresholds of 0, 1 and 3 (Table) were derived as an

ad hoc analysis. Absolute PASI response rates were significantly

higher for guselkumab vs. placebo at week 16 and vs. adali-

mumab at weeks 24 and 48. Among adalimumab-randomized

patients, PASI responses were substantially higher by week 76

following crossover to guselkumab at week 52. Skin response

levels were maintained through 2 years among guselkumab-

treated patients (Table). In conclusion, guselkumab treatment

provided significantly higher absolute PASI responses than

adalimumab through 1 year, and robust skin responses were

maintained through 2 years with continuous guselkumab

treatment.

P106Guselkumab treatment results in more effectiveand durable inhibition of T helper (Th)17 and Th22cells and downstream effectors compared withadalimumabX. Liu,1 P.J. Branigan,2 Y. Chen,1 S. DePrimo,1

K. Campbell2 and E.J. Munoz11Janssen Research & Development, LLC, San Diego, CA, U.S.A. and 2Janssen

Research & Development, LLC, Spring House, PA, U.S.A.Psoriasis is an interleukin (IL)-23-driven T-cell-mediated

inflammatory skin disease. Guselkumab (GUS) is a fully

human IgG1k monoclonal antibody that selectively binds and

blocks IL-23. In VOYAGE 1, a phase III study in patients with

moderate-to-severe chronic plaque psoriasis, GUS demon-

strated superior efficacy over adalimumab (ADA), a tumour

necrosis factor (TNF)-a inhibitor. To understand further their

underlying molecular mechanisms of action, microarray data

were generated from skin biopsies obtained at baseline and at

4, 24 and 48 weeks after initiation of GUS (n = 17) or ADA

(n = 12) treatment. GUS- and ADA- mediated normalization

of disease-associated gene expression was evaluated for a list

of curated immune/skin inflammation gene sets related to T

helper (Th)17, Th22, Th1, T regulatory cell (Treg), immune-

activated macrophage, dendritic cell, keratinocyte and epithe-

lial cell profiles. Gene set variation analysis (GSVA) was

applied to evaluate disease- and treatment-associated differen-

tial expression at the whole gene set level. In total 81 of 131

gene sets were enriched with differentially expressed genes at

baseline (lesional vs. nonlesional). In each of these 81 gene

sets, more genes were normalized by GUS than ADA at all

time points, with the greatest differences seen at week 48. At

4 weeks, 12 vs. 0 gene sets showed > 50% of genes with

> 75% improvement for GUS and ADA, respectively. At

48 weeks, 75 vs. 0 gene sets showed > 50% of genes with

> 90% improvement for GUS and ADA, respectively. The top

20 gene sets showing improvement included Th17-specific

genes, Treg-upregulated genes and IL17-, IL22-, IL17-/IL22-,

IL17- and TNF-a-induced genes in keratinocytes. GSVA con-

firmed 74 out of 81 gene sets and identified 40 additional

gene sets that were differentially expressed at baseline, includ-

ing a T-cell-receptor complex gene set that was more effi-

ciently normalized by GUS. Overexpression of T-cell-receptor

genes (TCRA, TCRB, CD3) was normalized with GUS by 20%,

62% and 102% at weeks 4, 24 and 48 compared with �19%,

25% and 21% by ADA, respectively. These data suggest that

the higher clinical responses observed with GUS compared

with ADA may result from more effective and durable inhibi-

tion of T cells, especially Th17 and Th22 cells, and down-

stream effects on keratinocytes.

P107Cost of topical therapies for patients with psoriasisin GeorgiaK. Tsagareishvili1 and N. Chijavadze21Akaki Tsereteli State University, Kutaisi, Georgia and 2Psoriasis Association

of Georgia (PSO Georgia), Kutaisi, GeorgiaPsoriasis is a chronic disease requiring prolonged treatment at

high cost. The goal of our research was to find out the cost of

topical treatment of the patients with mild-to-moderate psori-

asis and its impact on their monthly income. For this purpose

103 patients with psoriasis were interviewed including 47

(45.2%) female and 55 (54.8%) male, with 65 (63.1%) from

urban and 38 (38.9%) from rural populations. Overall 74% of

the patients were age 25–76 years. The diagnosis in 97.9% of

patients was mild-to-moderate chronic plaque psoriasis with

an affected body surface area < 10%. These patients used only

self-treatment with topic medications and had poor contact

with their dermatologists. The questionnaire included the type

and amount of topical medications used by the patients with

psoriasis, the frequency of showering, their skincare products

and their monthly income. The results showed that 99%

(102) of the patients used only the strongest strength of topi-

cal steroid – clobetasol propionate 0.05% (available over the

counter in Georgia) – not only for the period of exacerbation

but also during the remission to prolong it, using four to five

tubes (each 25 g) per month. At the same time as the topical

corticosteroid treatment, only 15 patients (14.6%) used other

topical medicines (calcipotriol 50 mg + betamethasone

500 mg ointment, coal tar solution 5%) because of their high

costs. The majority of the patients (71.4%, 74) did not use

skincare products; 70.6% of the patients showered every day

and 29.4% showered two to three times per week. The aver-

age income of the interviewed patients of the different income

groups varied from 72 USD (180 GEL) to 400 USD (1000

GEL). Accordingly the expenses of topical corticosteroid treat-

ment were highest among pensioners (16.7%), and 3–6%among the other groups. The low income of the patients, the

availability of over-the-counter topical corticosteroids in Geor-

gia, their low costs compared with other topical medicines

and their effectiveness determine the priority of their usage.

According to the National Statistics Office of Georgia, 21.3%

of the population was under the absolute poverty line in



2016, therefore further study of economic impact of the treat-

ment of psoriasis in Georgia would provide data on the

disease burden on society.

P108Looking beyond 12 weeks: long-term drug survivaland safety of secukinumab in real-world patientswith plaque psoriasisJ.R. Georgakopoulos,1 A. Ighani,2 M. Phung3 andJ. Yeung4,51Schulich School of Medicine and Dentistry, Western University, London,

ON, Canada; 2Faculty of Medicine, University of Toronto, Toronto, Canada;3Department of Pharmacology and Toxicology, University of Toronto,

Toronto, ON, Canada; 4Division of Dermatology, Faculty of Medicine,

University of Toronto, Toronto, ON, Canada and 5Probity Medical Research

Inc., Waterloo, ON, CanadaFrom early findings identifying interleukin (IL)-17A as a plau-

sible target in the immunopathogenic mechanism of psoriasis

to phase III randomized controlled trials (RCTs) demonstrating

secukinumab to be highly efficacious and safe, much excite-

ment has surrounded the approval of the first IL-17A antago-

nist. However, at this time, no study has looked at long-term

outcomes for real-world patients with psoriasis, who are

believed to be more challenging to treat than those enrolled

in RCTs. We aimed to investigate the efficacy and safety of

secukinumab at week 52 or the time of treatment discontinua-

tion for individuals who were Psoriasis Area and Severity

Index (PASI) 75 responders at week 12. These findings will

provide much-needed insight into whether real-world patients

with psoriasis achieve similar long-term outcomes to individu-

als enrolled in RCTs. A multicentre retrospective chart review

was conducted using data from medical records of adult

patients treated with secukinumab 300 mg for plaque psoria-

sis. Efficacy [PASI 75 or Physician’s Global Assessment (PGA)

of 0 or 1] and safety (reported adverse events) were assessed

following 12- and 52-week treatment periods or at the time

of discontinuation. Forty-one patients had moderate-to-severe

plaque psoriasis, achieved PASI 75 or PGA 0/1 at week 12

and were followed up to week 52 or the time of secukinumab

discontinuation, and thus were included in our analysis.

Twenty-eight (68%) maintained PASI 75 or PGA 0/1 at week

52. Of the 13 (32%) patients who did not achieve efficacious

outcomes at week 52, two (5%) experienced loss of efficacy

(< PASI 75) and 11 (27%) stopped treatment prior to week

52 due to lack of efficacy (n = 10, 24%) or intolerance

(n = 1, 2%). The mean treatment duration for individuals

who discontinued treatment between weeks 12 and 52 was

40.0 weeks (range 26.1–51.0). Additionally, adverse events

after week 12 were documented in 17% (n = 7) of patients.

Commonly reported adverse events included diarrhoea (n = 2,

5%) and respiratory tract infection (n = 2, 5%). Our results

suggest that fewer patients with psoriasis in real-world clinical

practice maintain efficacious outcomes at week 52 than those

enrolled in RCTs. Furthermore, discontinuation of treatment

appears to occur around week 40, similarly to time of treat-

ment discontinuation seen with older biological therapies.

Overall, these findings will greatly improve dermatologists’

ability to monitor secukinumab efficacy and safety beyond

week 12.

P109Efficacy and safety of ixekizumab in secukinumabnonresponders: therapeutic options for nonanti-interleukin-17A-naive patientsJ.R. Georgakopoulos,1 M. Phung,2 A. Ighani3 andJ. Yeung4,51Schulich School of Medicine and Dentistry, Western University, London,

ON, Canada; 2Department of Pharmacology and Toxicology, University of

Toronto, Toronto, ON, Canada; 3Faculty of Medicine, University of Toronto,

Toronto, ON, Canada; 4Division of Dermatology, Faculty of Medicine,

University of Toronto, Toronto, ON, Canada, 5Probity Medical Research Inc.,

Waterloo, ON, CanadaThe discovery of type 17 helper T (Th17) cells and their

release of the proinflammatory cytokine interleukin (IL)-17A

has shown that they play a central role in the autoimmune

inflammatory cascade and phenotypic changes associated

with psoriasis. New biological agents, secukinumab and

most recently ixekizumab, have been developed that bind to

IL-17A and neutralize the bioactivity of this cytokine. While

both have been vigorously studied in isolation, no study

has looked at outcomes when switching between these two

treatments, which have similar therapeutic targets. This is of

interest, as biological switching has become a common

practice in dermatology clinics. Consequently, we aimed to

assess the efficacy and safety of ixekizumab in real-world

patients with plaque psoriasis who have previously failed

secukinumab therapy. From secukinumab drug approval

until July 2017, we performed a multicentre retrospective

chart review of consecutive patients with psoriasis treated

with secukinumab 300 mg. Patients who were 18 years of

age or older with moderate-to-severe plaque psoriasis and

treated with ixekizumab 80 mg (160 mg at week 0, fol-

lowed by 80 mg every 2 weeks starting week 2), immedi-

ately following discontinuation of secukinumab due to lack

of efficacy or intolerance, were eligible for inclusion. Of

the 16 patients who met the inclusion criteria, 13 (81%)

achieved ≥ 75% improvement in Psoriasis Area and Severity

Index (PASI 75) after 12 weeks of ixekizumab treatment.

The mean PASI at secukinumab baseline was 13.0 � 4.7; it

was 11.0 � 3.4 at the time of switching and 1.6 � 3.6 at

ixekizumab week 12. Five (31%) patients experienced one

or more nonserious adverse event, including injection-site

reaction (n = 3, 19%), elevated liver enzymes (n = 1, 6%)

and drug eruption with lymphocytic and eosinophilic infil-

trates secondary to secukinumab (n = 1, 6%). Discontinua-

tion of treatment due to an adverse event was uncommon,

with just one patient (6%) stopping due to a prolonged

drug eruption secondary to secukinumab. Despite the inher-

ent limitation in our sample size, this is the first report of

the efficacy and safety of ixekizumab in nonanti-IL-17A-

naive patients. Our findings suggest that ixekizumab appears

to be a promising efficacious treatment option for





from gene to clinic

125ABSTRACTS

secukinumab nonresponders and is associated with a clini-

cally acceptable rate of adverse events.

P110Long-term, real-world efficacy of infliximab forpsoriasisL. Mercieca, R.B. Warren and C.E.M. GriffithsDermatology Centre, Salford Royal Hospital, University of Manchester,

Manchester, U.K.Infliximab has been licensed for the management of severe

psoriasis since 2006. There are limited data on its long-term,

> 6-year, efficacy. The aim of this study is to report long-

term, real-world clinical data of patients with psoriasis on

infliximab. A single-centre retrospective observational study

was conducted. Patients with psoriasis maintained on inflix-

imab for 6 years or longer were included. Clinical data,

including Psoriasis Area and Severity Index (PASI) and Derma-

tology Life Quality Index (DLQI), were collected prior to start-

ing infliximab and at each subsequent outpatient visit. A total

of 11 patients with psoriasis (seven male and four female)

with an average age of 54.5 years (range 43–81) were main-

tained on infliximab at 5 mg kg�1 every 6–8 weeks (average

7.6) for ≥ 6 years. The average age of onset of psoriasis was

24.2 years (range 11–61) and nine had psoriatic arthritis. The

most common comorbidities, other than psoriatic arthritis,

were hypertension, cardiovascular disease and ankylosing

spondylitis. Infliximab was started between 2005 and 2011

with a mean treatment duration of 9.2 years (range 6–12).The mean baseline PASI and DLQI scores were 22.4 and 18,

respectively. At years 1, 4, 8 and 12 the respective mean PASI

scores were 4.6, 1.9, 2.3 and 2.4, while the mean DLQI

scores were 3, 3, 4 and 4, respectively. There were no serious

side-effects reported, with recurrent respiratory and skin infec-

tions being the most common. Most patients flared up after

postponing treatment due to surgery, infections or time

abroad, and three patients were on concomitant low-dose

methotrexate (average dose 10 mg per week). To our knowl-

edge this is the longest reported study on patients with psoria-

sis maintaining efficacy and safety on infliximab for up to

12 years. Further studies are needed to elucidate why these

patients continue to have control of their psoriasis on long-

term infliximab.

P111Fine mapping and subphenotyping implicatesADRA1B gene variants in psoriasis in a ChinesepopulationX. Fan,1,2,3 H. Wang,1,2,3 L. Sun,1,2,3 X. Yin,1,2,3

X. Zuo,1,2,3 Q. Peng,4 K. A. Standish,5,6 X. Zheng,1,2,3

Z. Wang,1,2,3 F. Xiao,1,2,3 S. Yang,1,2,3 X. Zhang12,3

and N.J. Schork51Institute of Dermatology, Anhui Medical University, Hefei, China; 2Key Lab

of Dermatology, Ministry of Education, Anhui Medical University, Hefei,

China; 3Department of Dermatology, The First Affiliated Hospital of Anhui

Medical University, Hefei, China; 4Department of Molecular and

Experimental Medicine, The Scripps Research Institute, La Jolla, CA, U.S.A.;

5Human Biology, J. Craig Venter Institute, La Jolla, CA, U.S.A. and6Biomedical Sciences Graduate Program, University of California, San Diego,

La Jolla, CA, U.S.A.Previous genome-wide association studies (GWASs) have iden-

tified more than 40 independent genome-wide significant pso-

riasis susceptibility loci. We identified a genomic region on

5q33.3 harbouring variants associated with psoriasis in our

own GWAS and replication between the IL12B and PTTG1

genes. However, there are many potential causal variants in

this genomic region. To examine further the influence of vari-

ants in and around this region, we used the 1000 Genome

reference haplotypes to impute additional variants in the

region in our study samples to increase the marker density in

this region to 2171 genetic variants. We then used lasso-based

regression analysis to assess the independent contributions of

these variants to psoriasis and found evidence of association

for 62 of the 2171 single-nucleotide polymorphisms (SNPs)

in this region (seven SNPs around IL12B, 12 SNPs around

PTTG1 and 43 SNPs between the two genes). To evaluate these

62 SNPs further, we tested them for association with different

clinical psoriasis subtypes, psoriasis severity and psoriasis age

of onset. These analyses revealed slight differences between

the SNPs exhibiting associations based on the whole case–con-trol analysis and the subphenotype, cases-only analysis. The

most significant locus with the largest number of SNPs was

located in the ADRA1B gene, which is between the IL-12B and

PTTG1 genes in the 5q33.3 region. Variants in ADRA1B were

most strongly associated with the plaque subgroup, and

showed a stronger association with the moderate-to-severe

skin disease group and an earlier age at onset of psoriasis.

Using genome-wide complex trait analysis, the four indepen-

dently associated loci in the ADRA1B gene in total explained

39.5% of the phenotype variance of psoriasis under the

assumption of psoriasis prevalence of 0.2%. This highlights

the contribution of ADRA1B to psoriasis in the Chinese popula-

tion. We found no evidence to support the notion that vari-

ants in the IL12B and PTTG1 genes are associated with age of

onset of psoriasis in our study, suggesting that the IL12B and

PTTG1 genes might have only a weak relation to psoriasis.

However, we did find evidence that variants in the ADRA1B

gene residing between IL12B and PTGG1 are associated with

psoriasis. This could explain why variants in the region have

been found to be associated with psoriasis previously,

although more studies confirming this should be pursued.

P112Retrospective study of childhood psoriasisM.S. Zorko and O. TockovaUniversity Medical Centre Ljubljana, Ljubljana, SloveniaPsoriasis is a chronic immune-mediated inflammatory skin dis-

ease that occurs in about 3.5% of the general population. It

begins in childhood in approximately one-third of the cases.

Most children manifest with plaque-type psoriasis vulgaris,

and the most common trigger is an upper respiratory tract

infection. Up to 71% of children have a family history of pso-

riasis. Paediatric psoriasis can been associated with certain



comorbidities, such as obesity, hypertension, hyperlipidaemia,

diabetes mellitus and rheumatoid arthritis. Treatment is deter-

mined based on the severity of the disease and remains a chal-

lenge. We performed a retrospective study of children with

psoriasis, aged under 16 years, who have been hospitalized at

our clinics between 2013 and 2016. In total 24 children with

moderate-to-severe psoriasis (median Psoriasis Area and Sever-

ity Index 17.2 at the beginning of the hospitalization) were

hospitalized at our clinics between 1 January 2013 and 31

December 2016. It represented 3% of all dermatoses seen in

hospitalized children under the age of 16 years. Sixteen (67%)

patients had classic plaque psoriasis, five (21%) had guttate

psoriasis and three (12%) had other types of psoriasis (palmo-

plantar psoriasis, inverse psoriasis, psoriasis of the nails and

scalp). In four of the five children with guttate psoriasis,

streptococcal infection preceded the onset. A positive family

history of psoriasis (first- and second-degree relatives) was

present in 13 (54%) children. Comorbidities like arterial

hypertension, diabetes, hyperlipidaemia and arthritis, most

commonly described, were not found in our patients. Among

16 children with a resistant form of plaque psoriasis, seven

were treated with methotrexate and three with narrowband

ultraviolet B phototherapy. We observed good response to the

therapy and no serious side-effects (mean Psoriasis Area and

Severity Index 3.5 at the end of hospitalization). As previously

described in the literature, plaque psoriasis is the most com-

mon type of psoriasis in children, and this was also seen in

our study. The guttate form was the second most common

type and it was mostly associated with streptococcal infection.

Comorbidities, most commonly associated with psoriasis, were

not found in our young patients. Based on our experience,

narrowband ultraviolet B and systemic therapy with

methotrexate are valuable, safe and effective treatments in the

moderate-to-severe form of therapy-resistant psoriasis in chil-

dren. However, more evidence-based data are needed about

the effectiveness and long-term safety of such therapies in

children.

P113Immature progenitor cells are enriched in psoriasisepidermisA.-K. Ekman, C.B. Eding, I. Rundquist andC. Enerb€ackIngrid Asp Psoriasis Research Center, Link€oping University, Link€oping, SwedenPsoriasis is a chronic inflammatory skin disorder characterized

by a marked hyperproliferation of basal epidermal cells. It is

regarded as a T-cell-mediated disorder, but the role of ker-

atinocytes in the disease pathogenesis has re-emerged with

genetic studies identifying several keratinocyte-specific genes.

We have applied multicolour flow cytometry on epidermal

keratinocytes isolated from involved and uninvolved epidermis

to characterize the cellular phenotype of these proliferative

cells and to compare the cell subpopulations further. We iden-

tified a strikingly reduced percentage of cells positive for the

early differentiation marker cytokeratin 10 (K10), combined

with increased fractions of CD29+ and involucrin-positive cells

in psoriasis keratinocytes compared with normal cells. The

psoriasis keratinocytes also displayed an overall increased

expression of the stemness markers p63 (sevenfold), CD44

(2.7-fold) and CD29 (2.2-fold). Interestingly, these differ-

ences were primarily confined to K10+ cells. We hypothesized

that stimuli present in the psoriatic micromilieu may con-

tribute to the cellular immaturity. In normal keratinocytes, we

found that interleukin-22 increased the expression of p63,

CD44 and CD29 at both the mRNA and protein levels. Taking

the evidence together, we describe an overall more immature

phenotype of psoriasis keratinocytes compared with normal

keratinocytes, with an altered frequency of several subpopula-

tions and a distinct marker expression within these subpopula-

tions. This immature stem cell-associated phenotype is likely

to impact the cell proliferation and premature terminal differ-

entiation in psoriasis. Furthermore, our data suggest that inter-

leukin-22 links immunity to epithelial regeneration by acting

directly on keratinocytes to promote stemness.

P114PRINS long noncoding RNA regulates theexpression of interleukin-6 and CCL-5 by directinteractionJ. Danis,1,2 A. G€obl€os,1,2 L. Janov�ak,2

Z. Bata-Cs€org}o,1,2 L. Kem�eny12 and M. Szell1,31MTA-SZTE Dermatological Research Group, Szeged, Hungary and2Department of Dermatology and Allergology and 3Department of Medical

Genetics, University of Szeged, Szeged, HungaryCytosolic DNA fragments represent pathogen and danger-asso-

ciated molecular patterns and induce a cascade of innate

immune responses in cells. Excessive cytosolic DNA can

enhance chronic inflammation predominantly by activating

inflammasomes, thereby contributing to the pathogenesis of

chronic inflammatory diseases such as psoriasis. Psoriasis-asso-

ciated nonprotein-coding RNA induced by stress (PRINS) is a

long noncoding RNA, which has already been associated with

psoriasis susceptibility and cellular stress response; however,

its precise mechanism has been less studied. Recently, its regu-

latory role in the expression of the chemokine, CCL-5, was

reported, suggesting its anti-inflammatory function. The aim

of this study was to identify the role of PRINS in psoriasis-

associated inflammatory reactions, which could explain the

importance of its high expression in psoriatic uninvolved epi-

dermis. Transfection of the synthetic DNA analogue poly(dA:

dT) was used to induce inflammatory reactions in normal

human epidermal keratinocytes (NHEKs), and expression of

inflammatory cytokines was measured by real-time reverse-

transcriptase polymerase chain reaction and enzyme0linked

immunosorbent assay. Poly(dA:dT) induced the expression of

interleukin (IL)-1a, IL-b, IL-6, IL-8, IL-23 an tumour necrosis

factor (TNF)-a, and pretreatment with combined TNF-a and

interferon-c increased their expression further. The treatment

decreased the expression of PRINS in NHEKs. Overexpression

of PRINS during the treatment resulted in decreased IL-6

expression. CCL-5, showing a similar expression pattern to

IL-6, was recently shown to be directly regulated by PRINS, so





from gene to clinic

127ABSTRACTS

we proposed a similar mechanism for IL-6 regulation. We

performed an in silico analysis and found a 100-nucleotide-long

possible interaction site between the mRNA of IL6 and PRINS.

An in vitro binding assay confirmed this predicted interaction

with a very high affinity of PRINS binding to IL6 mRNA

(Kd = 10.34 nmol L�1). To validate the functionality of this

interaction on the cellular level we created a DPRINSsequence, containing a scrambled sequence on the possible IL6

interaction, site and performed the overexpression experiment

with DPRINS. While PRINS decreased the expression of IL6,

DPRINS did not show the same effect; however, the level of

CCL-5 (having a different interaction site) decreased to the

same level after overexpression of PRINS or DPRINS. Based on

our results we propose that PRINS acts as a regulator for both

IL-6 and CCL-5. These results link PRINS to inflammatory pro-

cesses, and indicate the significance of its higher expression in

psoriatic uninvolved epidermis. Funding: K111885, GINOP-

2.2.1-15-2016-00007 and GINOP-2.3.2-15-2016-00015.

P115CARD14 variants in pityriasis rubra pilarisA. G€obl€os,1,2 J. Danis,1,2 B. G�al,1 K. Farkas,3

E. Varga,1 I. Korom,1 L. Kem�eny,1,2 N. Nagy,3

M. Sz�ell23 and Z. Bata-Csorg}o1,21Department of Dermatology and Allergology and 3Department of Medical

Genetics, University of Szeged, Szeged, Hungary and 2MTA-SZTE

Dermatological Research Group, Szeged, HungaryPityriasis rubra pilaris (PRP) is a rare, papulosquamous skin

disorder with important inflammatory features. PRP is pheno-

typically related to psoriasis. CARD14 single-nucleotide variants

(SNVs) have been described in both diseases, and documented

gain-of-function CARD14 mutations suggest its role in the dis-

ease pathomechanism. We screened 15 patients with sporadic

PRP and one with familial PRP for SNVs in the CARD14 gene.

In the patient with familial PRP we identified three genetic

variants (rs117918077, rs2066964, rs28674001), while con-

trol individuals (three healthy and two psoriatic volunteers)

carried the wild-type alleles. Of the 15 patients with sporadic

PRP, eight carried SNVs. In all of them only two types of

polymorphisms were detected either alone or in combination

(rs2066964 and rs28674001). Additionally, in three patients

we detected mutations in the CARD14 gene (rs2289541,

rs34367357, c.1198_1199CG/TA). Further in vitro and in situ

functional studies were carried out in the patient with familial

PRP to examine the functional relevance of the genetic vari-

ants. Immunofluorescent staining revealed nuclear localization

of the nuclear factor (NF)-jB p65 subunit in the PRP skin

specimen, indicating activated NF-jB, in contrast to healthy

and psoriatic skin sections where only cytoplasmic staining of

inactivated NF-jB was shown. An NF-jB luciferase reporter

assay demonstrated significantly increased NF-jB activity in

keratinocytes from the patient with PRP compared with

healthy keratinocytes. Characterization of the cytokine profile

of the keratinocytes and peripheral blood mononuclear cells

demonstrated that the higher NF-jB activation in PRP cells

induced higher responses to inflammatory stimuli compared

with healthy cells. Our study indicates the importance of

CARD14 in patients with PRP and highlights that functional

characterization of rare and common variants of the CARD14

gene can bring us closer to understanding the role of genetic

variants in disease pathogenesis. Funding: K111885, GINOP-

2.3.2-15-2016–00015 and GINOP-2.2.1-15-2016-00007

P116Early changes in peripheral leucocyte populationsduring oral dimethylfumarate treatmentP. Morrison, D. St€olzl, S. Kurras, S. Gerdes andU. MrowietzUniversit€atsklinikum Schleswig-Holstein, Kiel, GermanyDimethylfumarate (DMF) is a common first-line drug used for

the treatment of moderate-to-severe psoriasis. The immuno-

suppressive effect of DMF is associated with a reduction in the

peripheral blood lymphocyte count, which, when uncon-

trolled, can result in severe lymphopenia. However, early

changes in the leucocyte compartment are relatively unre-

ported. Thus, in the current study we have assessed the

changes in blood leucocytes in a cohort of patients with psori-

asis during the first 3 months of DMF treatment. Using multi-

colour flow cytometry we assessed the frequencies of CD4 and

CD8 T cells and neutrophils. Our results showed that the

majority of DMF-treated patients had a reduction in absolute

leucocytes after only 1 month of treatment. When analysed in

detail we found that a loss of peripheral neutrophils was pri-

marily responsible for this reduction, particularly in the first

month of treatment. In most patients, the reduction in neu-

trophils persisted at all time points. - cell counts were gener-

ally increased compared with baseline after 1 month of

treatment. Hence, the number of peripheral CD3+ T cells was

increased in 69% of patients with a mean increase to

158.3 � 36.7% of the pretreatment baseline. Increases in both

CD4 and CD8 T cells accounted for this change. At the same

time point, a drop in the number of T cells was seen in 23%

of patients, with a mean decrease to 57.7 � 17.1% of the

pretreatment value. Both CD4 and CD8 T cells were reduced.

The losses in peripheral T-cell number were more prevalent

by month 3, when 61.5% of patients had a reduced CD3

T-cell count, with a mean decrease to 55.6 � 13.6% of base-

line. Again, both CD4 and CD8 T cells were affected, with

CD4 T cells at 56.5 � 14% compared with baseline and CD8

T cells at 52.7 � 19.7%. However, no patients were consid-

ered lymphopenic by month 3, as all had a CD3 count

> 0.5 9 109 cells L�1. The remaining 38.5% of patients dis-

played a mean relative increase in CD3 T-cell count to 132.7%

of baseline, with both CD4 and CD8 cells increased. Our data

show that neutrophils are affected by oral DMF from an early

time point, while it takes longer for T cells to be reduced. As

neutrophils are critical for psoriasis pathogenesis, it is likely

that these changes are linked to the disease ameliorating effect

of DMF.



P117Randomized controlled trial of patient-initiatedcare for patients with psoriasisL. Khoury,1 T. Møller,2 C. Zachariae1 and L. Skov11Department of Dermatology and Allergy, Herlev and Gentofte Hospital,

University of Copenhagen, Copenhagen, Denmark and 2University Hospitals

Centre for Health Care Research, Rigshospitalet, University of Copenhagen,

Copenhagen, DenmarkTreatment and care of moderate-to-severe psoriasis often

require lifetime consultations by dermatologists with close

monitoring of systematic treatment. Moreover, psoriasis is a

fluctuating disease and the patient’s healthcare needs depend

on the current severity of their psoriasis, indicating that

healthcare services plays a more significant role during some

periods of patients’ lives. We hypothesize that a more flexible

system may reduce inappropriate follow-up consultations,

release resources to difficult consultations, and improve patient

quality of life and satisfaction with healthcare. We therefore,

aimed to determine the effect of patient-initiated care (PIC)

for patients with psoriasis in a dermatology outpatient clinic.

A prospective randomized controlled trial was set up. Patients

on well-controlled systemic treatment were randomly assigned

to either (i) the PIC group, where patients received one yearly

scheduled consultation with a dermatologist and with no rou-

tine follow-up consultations, but patients were able to initiate

consultations when needed or (ii) the control group, where

patients received consultation routinely every 12–16 weeks.

The main outcome was Dermatology Life Quality Index

(DLQI), and secondary outcomes were clinical status, safety

and patient satisfaction with healthcare assessed at baseline

and after 1 year. In total 150 patients were included in the

study (73 in the PIC group and 77 in the control group).

Overall 58.0% were treated with biologics, 37.3% with

methotrexate and 4.7% with acitretin. Patients in the PIC

group requested a mean � SE of 2.46 � 0.13 consultations

vs. 5.05 � 0.61 in the control group, corresponding to

64.2% fewer appointments for the PIC group over 1 year

(P = 0.001). Having fewer consultations did not decrease

safety for patients in the PIC group, and no statistical signifi-

cantly mean difference was detected for Psoriasis Area and

Severity Index, 0.08 � 0.23 vs. �0.16 � 0.2 (P = 0.42), or

laboratory control, 0.21 � 0.67 vs. 0.21 � 0.47 (P = 0.093)

in the PIC and control groups, respectively. Patients reported

high satisfaction with healthcare, and no significant mean dif-

ferences were observed between groups regarding satisfaction

with overall care (P = 0.24), treatment (P = 0.75) and infor-

mation (P = 0.09). There was also no change in DLQI:

0 � 0.22 vs. 0.28 � 0.23 (P = 0.38). PIC offers some clinical

benefits compared with routine care, giving patients more

flexibility and less dependence on doctors and clinical visits.

The intervention adds no harm to monitoring systematic pso-

riasis treatment, and patients report high quality of life and

satisfaction with healthcare. Avoiding unnecessary consulta-

tions releases resources to organize a more patient-centred

approach to dermatology services, providing time to support

patients during vulnerable periods and psoriasis relapse, and

decrease comorbidity risk. This study has been registered with

Clinicaltrials.gov, file no. NCT02382081.

P118Establishment of an intradermal ear injectionmodel of interleukin (IL)-17A and IL-36c as a toolto investigate the psoriatic cytokineD. Kluwig, S. Huth, C. Pfaff, L. Huth, Y. Marquardt,K. Fietkau, J.M. Baron and B. L€uscherUniklinik RWTH Aachen, Aachen, GermanyPsoriasis is a chronic skin disease caused by the excessive

secretion of inflammatory cytokines, and affects 2–3% of the

Western population. The proinflammatory interleukin (IL)-

17A is a key cytokine in psoriasis. However, accumulating evi-

dence has revealed that IL-36c also plays a pathogenic role in

this disease. So far, using keratinocyte monolayers and a

three-dimensional psoriasis model we have already detected a

feedback loop between the IL-17 and IL-36 cytokines that

induces and maintains psoriasis pathology. To understand

more precisely the role of the IL-17A–IL-36c cytokine net-

work in skin pathology, we used an ear injection model in

our present study. Therefore, we injected IL-36c and IL-17A

alone or in combination into the ear pinnae of mice. After

4 days of consecutive treatment mice were euthanized and

histological and immunohistological stainings were performed.

The intradermal delivery of IL-17A and IL-36c resulted in a

significant increase of the ear thickness measured over time.

Histological evaluation of IL-17A- and IL-36c-treated skin

showed a strong acanthosis accompanied by hyperkeratosis

and spongiosis. We found the same histological features in

mice that underwent injections with IL-36c alone, but to a

lesser extent. IL-17A on its own was not able to induce psori-

asis-like changes in the mouse skin. Moreover, the expression

of genes encoding antimicrobial peptides, like mS100A8,

mDEFB4 (orthologue of human b-defensin 2), mS100A7A

and mDEFB14 (orthologue of human b-defensin 3) were

upregulated after treatment with IL-17A and IL-36c in combi-

nation. Similar effects were partially seen after the injection of

IL-17A and IL-36c alone, but the expression was much

weaker. In conclusion, intradermal injection of IL-17A and

IL-36c in the ear pinnae of mice provides an in vivo model to

investigate psoriasis. Our results strengthen the thesis that

IL-17A and IL-36c drive psoriatic inflammation via a synergis-

tic interaction. Our established intradermal ear injection model

of IL-17A and IL-36c can be utilized in future to monitor

effects of various inhibitors of this cytokine network.

P119Pharmacogenomic signature of response togenistein therapy for psoriasis: effects of genisteinin vitro and in vivo and its mechanism of actionE. Smoli�nska,1 M. Moskot,1,2 K. Boche�nska,1

A. Lewczuk,3 T. Brodniewicz,3 J. Jak�obkiewicz-Banecka1 and M. Gabig-Cimi�nska1,21Department of Medical Biology and Genetics, University of Gda�nsk, Gda�nsk,

Poland; 2Institute of Biochemistry and Biophysics, Polish Academy of





from gene to clinic

129ABSTRACTS

Sciences, Laboratory of Molecular Biology (affiliated with the University of

Gda�nsk), Gda�nsk, Poland and 3MTZ Clinical Research Sp. z o.o., Warsaw,

PolandPharmacogenomics has the potential to facilitate the develop-

ment of safer and more effective drugs in terms of their benefit

and/or risk profiles. Genistein, a soy-derived isoflavone, has

attracted attention as a potent agent in the treatment of psoriasis.

It is also known as an agent modulating expression of various

genes. The aim of the current study was to perform the first

pharmacogenomic study on genistein treatment in an in vitro

model of human keratinocyte culture, and also in patients with

psoriasis in the Polish population (lesional and nonlesional skin,

and blood) using mRNA expression profiling of genetic markers

to assess prediction of response to drug therapy. For the in vitro

study, the cytotoxic and antiproliferative activities of genistein

against keratinocytes were tested. The effect of the anti-inflam-

matory and antipsoriatic activity of genistein on gene expression

was investigated by culturing human epidermal keratinocytes

under inflammation-inducing conditions. The involved sig-

nalling pathways were studied by treating the cells with specific

inhibitors. Global gene expression profiling was performed, fol-

lowed by dedicated real-time quantitative reverse-transcriptase

polymerase chain reaction (qRT-PCR) custom panel analyses for

identification of activity of genistein-responsive genes. Assess-

ments were made of phosphoinositide 3-kinase activity, nuclear

factor-jB translocation, activation of reactive oxygen species,

and inflammatory cytokine levels following genistein treatment.

For the in vivo study, participants underwent detailed phenotyp-

ing and were assessed about their response to therapy using the

Psoriasis Area and Severity Index, body surface area involvement

and Physician’s Global Assessment. Skin biopsy and blood sam-

ples were collected at two time points: at baseline and after

56 days of therapy. Dedicated real-time qRT-PCR custom panel

analyses for identification of activity of genistein-responsive

genes were performed on RNA extracted from lesional and non-

lesional skin, and blood samples (n = 4). Efficacy studies of

genistein action were made via determination of interleukin

(IL)-12, IL-17, IL-23 and tumour necrosis factor-a levels. Test-

ing the effects of genistein on the human cell transcriptome, we

found that this compound significantly modulated activities of

psoriasis-like transcripts, by reducing the expression efficiency

of genes revealing enhanced activity in psoriatic cells, and by

stimulating the expression efficiency of genes revealing

decreased activity in psoriatic cells. Treatment with genistein

was safe and well tolerated with no significant changes. A psori-

asis screening qRT-PCR array has been developed for monitor-

ing of patients with psoriasis undergoing isoflavone therapy.

P120Itch and pain perception and epidemiology inpatients with psoriasis: results from a prospectivetwo-centre studyN. Max,1 K. Torz,1 U. Mrowietz,1 V. Oji,2 S. St€ander3

and S. Gerdes1

1Psoriasis-Center, Department of Dermatology, University Medical Center

Schleswig-Holstein, Campus Kiel, Kiel, Germany; 2Department of

Dermatology, University Hospital M€unster, M€unster, Germany and 3Center

for Chronic Pruritus, Department of Dermatology, University Hospital

M€unster, M€unster, GermanyTo treat psoriasis it is necessary to achieve a therapeutic alliance

with the patients. Thus, patient-related aspects should be taken

into account. A crucial and life-quality-reducing symptom of

psoriasis is pruritus, and recent studies show that itching is the

predominant symptom in the patient’s awareness of disease.

Clinical comparison with other dermatoses suggests differences

in the characteristics of pruritus, for example as patients with

psoriasis rarely present skin artefacts due to scratching. Specific

investigations on different skin symptoms and the frequency,

location and onset of pruritus are missing. In order to improve

patient management, we have characterized the clinical aspects

of pruritus at two specialized psoriasis centres in Germany. In

total 282 were been included in this prospective study. During a

face-to-face interview, both a self-developed and multiple speci-

fic itch questionnaires (including ItchyQoL) were used to assess

the perception and epidemiological data of pruritus within this

patient cohort. The mean age was 49.5 � 14.9 years and the

mean Psoriasis Area and Severity Index was 5.21 � 6.92,

reflecting that patients were moderately affected by psoriasis.

Pruritic symptoms were reported by 59.9% of all patients. In

total 37.2% of the patients reported that the onset of any pruritic

symptoms was either coincident with or after psoriasis onset.

Overall 60.3% of the patients were able to localize their itch.

Three-quarters (73.5%) of these patients felt symptoms only

within psoriatic lesions, whereas only 12.4% of the patients also

experienced perilesional itch. Another 12.4% of the patients

reported itch all over their body, while only 1.7% of the patients

had itch in unaffected skin only. Of all patients who reported on

itch frequency (n = 170), 63.5% had symptoms during five or

more days a week. Only 22.9% of the patients had symptoms

on less than 3 days per week. Out of 170 patients, 54.7% had

skin pain instead of itch and 79 patients stated that they were

able to differentiate clearly between itch and skin pain symp-

toms. In total 60.8% of 176 patients reported on an impact on

interpersonal relationships and 64.8% have had sleep distur-

bances. In conclusion, this study underlines the high frequency

and importance of pruritic symptoms in patients with psoriasis

and reveals a strong relationship with psoriatic lesions. The

symptom of skin pain could be distinguished from itch by

almost half of the patients, supporting the idea of a specific pso-

riasis itch that should be investigated in more detail.

P121Body locations of difficult-to-treat psoriasis in theera of treatment with biological agents: a Danishmulticentre studyK.F. Hjuler,1 L. Iversen,1 K. Kofoed,2 M. Rasmussen,1

L. Skov2 and C. Zachariae21Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark

and 2Department of Dermato-Allergology Gentofte Hospital, University of

Copenhagen, Copenhagen, DenmarkTraditionally, psoriasis in certain body sites has been acknowl-

edged as difficult-to-treat variants. Such locations are the scalp,



nails, palms, soles and intertriginous areas. During the last

decade, several highly effective systemic agents have been

approved for the treatment of psoriasis. Despite the availability

of these novel agents, the same areas are still considered diffi-

cult to treat. To our knowledge, no published studies have

examined the location of recalcitrant psoriasis in patients trea-

ted with biological agents. The aim of this study was to inves-

tigate the location of treatment-refractory psoriasis in patients

treated with biological agents in real-world clinical practice. In

this observational study we investigated the skin and/or nail

location of treatment-refractory psoriasis in patients with

moderate-to-severe psoriasis treated for > 6 months with bio-

logical agents approved for the treatment of psoriasis with a

partial or good response to treatment and a Psoriasis Area and

Severity Index (PASI) 1–5. Experienced PASI assessors in two

university hospital dermatology clinics included patients con-

secutively in the database. Both sites used a uniform data col-

lection method predefined in a data entry form in which the

body area was divided into 26 regions and 20 nails. Between

May 2017 and August 2017 we included 111 patients with

chronic plaque-type psoriasis: 75.0% men, mean age

50.7 � 13.3 years, with a median PASI score of 2.4,

interquartile range (IQR) 1.2–3.4. The most commonly used

biological agent was ustekinumab (35.1%). The median dura-

tion of treatment with biologics was 48 months (IQR 12–84).The median PASI reduction from treatment initiation was

86.1% (IQR 78.4–91.7). The most common site of recalcitrant

psoriasis in this cohort of patients treated with biological

agents was the anterior lower leg region [49.5%, 95% confi-

dence interval (CI) 40.2–58.9]. Further common sites of

recalcitrant psoriasis were the posterior lower leg region

(22.5%, 95% CI 14.8–30.3), the elbow region (36.0%, 95%

CI 27.1–45.0) and the scalp (18.9%, 95% CI 11.6–26.2).Regarding the body regions traditionally considered as diffi-

cult-to-treat sites the proportions of patients with recalcitrant

psoriasis were fingernails 11.7% (95% CI, 5.7–17.7), toenails12.5% (95% CI 6.1–18.9), scalp 18.9% (95% CI 11.6–26.2),palmar region 3.6% (95% CI 0.1–7.1), plantar region 0.9%

(95% CI �0.9 to 2.7) and intertriginous areas 9.0% (95% CI

3.7–14.3). In conclusion, in real-world clinical practice, the

most common sites of recalcitrant psoriasis in patients treated

with biological agents are the anterior crural region, the pos-

terior crural region and the elbows. The regions traditionally

accepted as difficult-to-treat areas were rarely affected with

recalcitrant lesions, although the scalp was often not clear.

P122The effect of monomethylfumarate on human bloodneutrophilsI. Suhrkamp, A.-S. Erkens, P. Morrison andU. MrowietzPsoriasis-Center Kiel, Department of Dermatology, University Medical Center

Schleswig-Holstein, Campus Kiel, Kiel, GermanyFumaderm, a mixture of fumaric acid esters, has been used to

treat psoriasis for more than 20 years. It was shown that

monomethylfumarate (MMF), the active metabolite of

Fumaderm’s main component, dimethylfumarate, binds to

hydroxycarboxylic acid receptor 2 (HCA2). As neutrophils

play a major role in the pathogenesis of psoriasis, we investi-

gated the effects of MMF on human neutrophils. By flow

cytometry we studied neutrophil counts in the blood of

patients with psoriasis taking Fumaderm. Most patients

showed a drop in neutrophil count in the first 3 months after

starting treatment. We assessed HCA2 expression by human

blood leucocytes and found that in contrast to T cells, B cells

and eosinophils, neutrophils expressed HCA2 protein on their

surface. In vitro stimulation of neutrophils revealed that HCAR2

mRNA expression could be upregulated by interferon-c. TheHCA2 receptor agonists MMF and nicotinic acid did not

change HCA2 transcript levels. In contrast, nicotinic acid and

MMF were able to reduce HCA2 surface protein levels when

analysed by flow cytometry, indicating that MMF can cause

agonist-induced internalization of HCA2. To determine

whether the neutrophil drop seen during fumarate treatment

was due to the induction of apoptosis, we stimulated human

neutrophils with MMF in vitro and assessed the rate of apopto-

sis using annexin V staining. We found that MMF did not

increase the rate of apoptosis in neutrophils when compared

with vehicle-stimulated samples. Using a Proteome Profiler

Array we assessed whether MMF could induce any apoptosis-

related signalling pathways in neutrophils. In agreement with

our annexin V results we found that MMF did not induce

phosphorylation of any apoptosis related-proteins. HCA2 ago-

nists have been reported to inhibit the forskolin-induced accu-

mulation of intracellular cAMP. Thus we investigated whether

MMF could have a similar effect; however, we found that

MMF caused a small nonsignificant decrease in cAMP in for-

skolin-activated neutrophils. We determined that MMF was

unable to induce a calcium flux in neutrophils. These data

indicate that the drop in blood neutrophils observed in Fuma-

derm-treated patients with psoriasis is not due to direct induc-

tion of neutrophil apoptosis. Therefore, other indirect

mechanisms that alter the size of the blood neutrophil

population must exist. The internalization of HCA2 in

response to MMF by neutrophils indicates that there are

downstream signalling events occurring, but that these do not

appear to be linked with changes in the second messengers

cAMP and calcium.

P123Psychological distress in patients using systemictherapies for psoriasis: the role of beliefs aboutillness and anger suppressionR. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft,L. Cordingley and on behalf of the PSORT studygroup and BADBIRUniversity of Manchester and Manchester Academic Health Science Centre,

Manchester, U.K.High levels of psychological distress can influence long-term

outcomes for people with psoriasis via psychophysiological

and behavioural pathways such as alcohol use or nonadher-

ence to medication. Beliefs about illness affect how people





from gene to clinic

131ABSTRACTS

cope and adjust to psoriasis, but few studies have explored

these relationships in those using biological therapies. We

assessed levels of general and psoriasis-specific psychological

distress and levels of anger experience in patients using con-

ventional systemic and biological therapies. We evaluated fac-

tors associated with distress using regression analyses. Cross-

sectional data from 811 patients using conventional systemic

and biological therapies for the treatment of moderate-to-

severe psoriasis and enrolled in the British Association of Der-

matologists Biologic Interventions Register (BADBIR) were

collected from 35 dermatology centres across England. We

measured anger expression (State-Trait Anger Expression

Inventory), distress (Hospital Anxiety and Depression Scale;

HADS), beliefs about psoriasis (Revised Illness Perception

Questionnaire) and medication (Beliefs about Medicines Ques-

tionnaire). A score ≥ 8 on the HADS indicates a possible or

probable caseness of anxiety and/or depression. High propor-

tions of the sample were classified as possible or probable

caseness for anxiety (40%) and/or depression (24%), with

two-thirds reporting strong negative psoriasis-specific distress

and almost half (47%) reporting strong feelings of anger

towards their psoriasis. In total, 11.5% reported a high level

of anger suppression. Stronger suppression of anger was asso-

ciated with anxiety (standardized b = 0.40, P ≤ 0.001),

depression (b = 0.40, P ≤ 0.001) and negative psoriasis-speci-

fic distress (b = 0.11, P = 0.001). Holding strong beliefs that

psoriasis has negative consequences was associated with nega-

tive psoriasis-specific distress (b = 0.49, P ≤ 0.001). There

were different drivers of anxiety and depression with worries

about appearance associated with anxiety (b = 0.13,

P = 0.006), whereas concerns that psoriasis is noticeable to

others was associated with depression (b = 0.17, P ≤ 0.001).

Patients who expressed the strongest medication concerns

were more likely to report higher depression scores

(b = 0.10, P = 0.002). Psychological distress remains high for

many patients using systemic therapies. Some patients using

biologics may require additional interventions to target long-

held beliefs and address emotion-focused coping strategies in

order to improve clinical outcomes and quality of life.

C.E.M.G. is a National Institute for Health Research Senior

Investigator. PSORT is funded by the Medical Research Coun-

cil, grant MR/1011808/1.



NOTES



from gene to clinic

133

Author Index

© 2017 The AuthorsBJD © 2017 British Association of Dermatologists British Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4 1

van Aarle, F., P004 Abe, N., P096 Abram, K., P097 Agada, N., P014 Ahn, R., P038 Ainscough, J., P009 Alase, A., P009 Alashqar, M., P010 Alikhan, M., P016 Anandan, A., P019 Andersen, A.-M.N., P100 Antoniou, C., P055 Arakawa, A., FC05, FC17, P066 Arakawa, Y., FC05 Arenberger, P., P021 Arendt, C., FC32 Armstrong, A., P003 , P103 Ashcroft, D., P078, P086, P101, P123 Asmawidjaja, P., FC27, P063, P064, P065 Augustin, M., FC21, FC26, FC30, P021, P044,

P104

Bachelez, H., FC20, P032 Baeten, D., P065 Bagel, J., FC29 Baker, C., P020 Banecka, J.J., P023 Bangert, C., FC33 Barbarot, S., P032 Barker, J., FC23, FC24, P002 , P052 Baron, J., P049 , P118 Barron, M.J., P084 Barry, J., FC22 Baskan, E.B., P041, P042 Bassukas, I., P055 Bata-Csörgo, Z., FC24, P114, P115 Bayaraa, B., P082 Beamer, M., FC25 Belkhodja, C., FC18 Beneton, N., P032 Benezeder, T.H., P079 Berends, M., P083 Berggren, L., P092 Bertelsen, T., P048 Besgen, P., P066 Bewley, A., P003 Beylot-Barry, M., P032 Bianchi, L., P040 Bisoendial, R., FC27, P064, P065 Bissonnette, R., FC31, P085 Blauvelt, A., FC29, FC32, P004, P022, P105 Blegvad, C., P100 Bochenska, K., P023, P119 Boehncke, W.-H., P003 van den Bogaard, E., FC04 Bomas, S., P017 Boon, L., P063 Bøttcher, M., P102 Boutouyrie, P., FC20 Bouwstra, J., FC04 Branigan, P.J., P106

de la Brassinne, M., P070 den Braanker, H., P064 Bravard, P., P032 Bridgewood, C., P089 Brodmerkel, C., FC08 Brodniewicz, T., P119 Broesby-Olsen, S., P075 Brooke, M., FC14 Brown, G., P009 Bryld, L.E., P075 Bukhalo, M., FC29 Bulfone-Paus, S., P084 Bundy, C., FC21 Bunton, D., FC22 Burden, D., FC23, FC24 , P052 Burge, D., FC32 Burkhardt, N., P092

Cai, S., P072 Calimlim, B., P029 Callis Du ffi n, K., FC12 Camez, A., FC29 Campbell, K., FC08, P106 Capon, F., FC24, P002 Carr, M.J., P078 Catapano, M., P002 Chadoutaud, B., P087 Chakravadhanula, U., P061, P067, P090 Chandrashekar, B.S., P090 Chaparro, D., P081 Charifa, O.S., P037 Chasapi, V., P055 Chen, J.-Q., P072 Chen, M., P073 Chen, W., P025 Chen, X., P073 Chen, X.-B., P072 Chen, Y., P106 Cheuk, S., FC19 Cheung, S.T., P028, P028 Chijavadze, N., P107 Chikh, A., FC14 Choon, S.E., FC24 Chosidow, O., P032 Ciccarelli, F., P002 Classon, C., FC19 Connolly, A., P034 Conrad, C., FC18 Cordey, M., FC21 Cordingley, L., P101, P123 Correia, E., P024 Cortes, C., P081 Cueto, I., P013

D’Adamio, S., P040 Dam, T., P075 Dand, N., FC07 Danis, J., P114, P115 Davelaar, N., FC27, P064, P065 Davey, P., P020 Dekker, E., P003

Delaporte, E., P032 Demaria, O., FC03, FC18 Deng, J., P006 DePrimo, S., P106 DeShazo, R., P062 Dewey, F., FC12 Di Domizio, J., FC03, FC18 DiMeglio, P., P034 Dizman, D., P041, P042 Djamei, V., P044 Dodds, M., P073 Dossenbach, M., P094 Drew, J., FC32 Driessen, R., P083 Du, S., P088 Du ff us, K., FC15 Dupuy, A., P032 Duric, M., FC22 Dutronc, Y., P094 Dutz, J.P., P039

Ebongo, C., P076, P077 Eding, C.B., P098, P113 Egeberg, A., FC01, FC28, P074, P075 Eidsmo, L., FC19 Ejarque, R.A., FC09 Ekman, A.-K., P098, P113 Elder, J., FC04, FC16 , P038 Ellinghaus, D., P038 Emsley, R., P101, P123 Enerbäck, C., P098, P113 Enk, A., FC11 Erkens, A.-S., P122 Erkılıc, A.C., P041, P042 Ewald, D.A., P099 Eydieux, C., P087 Eyerich, K., FC21 Eyre, S., FC15

Fakharzadeh, S., P062 Fan, X., P111 Farkas, K., FC24, P115 Fathy, M., P060 Fazeli, A., P097 Fearnley, G., P089 Fei, C., P025 Feng, B.-J., FC12 Fernández-Peñas, P., P003, P092 Festini, T., P029 Fietkau, K., P049, P118 Finlay, A., FC23 Fitz, L., P088 Flack, M., FC29 Florencia, E., P063 Foerster, J., P038 Foley, P., P053 Foo, M., FC06 Fotiadou, C., P031 Franke, A., P038 Frankel, E.H., FC29 French, L., FC18

AUTHOR INDEX

2 Author Index

© 2017 The AuthorsBritish Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4 BJD © 2017 British Association of Dermatologists

Frey, S., FC10 Fries, A., FC03 Frueh, J., P021, P026 Fuentes-Duculan, J., P013 Furnholm, T., FC06

Gabig-Ciminska, M., P023, P119 Gál, B., P115 Galindo, C., P062 Galinski, A., FC05 Galluzzo, M., P040 Garcet, S., FC08, P013 Geng, Z., FC29 Georgakopoulos, J.R., P056, P057, P080,

P108, P109 Gerber, S.J., P073 Gerdes, S., FC10, P116, P120 Ghislain, P.-D., P070 Giboin, C., P032 Gilliet, M., FC03 , FC18 Gkogkolou, P., FC10 Gniadecki, R., P075 Göblös, A., P114, P115 Golbari, N., P091 Goldblum, O., P092 Goldgar, D., FC12 Goldstein, N., P010 Gong, Y., P025 Gonzaga-Jauregui, C., FC12 Gooderham, M., FC29, P104 Good fi eld, M., P009 Goodhead, C., P071 Gordon, W., P088 Gormsen, L.C., FC28 Gottlieb, A., FC32, P014, P026 Goyal, K., P062 Graham, A., P089 Gri ffi ths, C.E.M., FC21, FC23, FC24, P022,

P051, P052, P053, P078, P084, P086, P101, P105, P110, P123

Griewank, K.G., FC10 Grine, L., P059, P070 Groegel, K., P017 Grünthaler, V., P007 Gu, Y., FC29, P068 Gudjonsson, J., FC25 Guo, J.-Z., P027 Gürer, M.A., P041, P042 Guthery, S., FC12

Hü ff meier, U., FC10 Hambro, C., FC16 Hamdidouche, I., FC20 Hamdy, S., P060 Hammer, K., P079 Hampton, P., P052, P071 Han, L., P006 Hassam, B., P076, P077 Hatchard, C., FC23 Hawkes, J., FC12 Hazes, J., FC27, P064, P065 Helder, R., FC04 Helliwell, P., P009 Henderson, J., FC06 Hendriks, W., FC04 Henneges, C., P094 Heppt, F., P008 Hesselvig, J.H., P074

Hillary, T., P070 Hirano, H., P096 Hjuler, K.F., FC28, P102, P121 Hofman, A., FC27 Hollister, K., P094 Hu, Y., P073 Huang, Y., P006 Huneault, L., P003 Hunter, H.J., P051 Hussain, A., P011 Huth, L., P118 Huth, S., P118

Ighani, A., P056, P057, P058, P080, P108, P109

Ilona, S.E., P035 Imafuku, S., P082 Inzinger, M., FC33 Ioannides, D., P031, P055 Irvine, A., FC24 Iversen, L., FC28, P047, P048, P102, P121

Jabbar-Lopez, Z.K., P051 Jacobi, A., FC10 Jagun, O., P028, P028 Jakóbkiewicz-Banecka, J., P119 James, E., FC17 Janovák, L., P114 Jansen, P., FC04 Jaquet, J.-B., FC27 Jarvis, P., P024 Jarvis, S., P003 Jauslin, P., P011 Jazayeri, S., P021 Je ff ery, P., FC23 Jha, B.K., P061, P067 Jiang, G., P103 Johansen, C., P047, P048 Johnston, A., FC06, FC16 Joly, P., P032 de Jong, E., P083, P093 Joshi, S.D., P001 Jullien, D., P032

Kahlenberg, M., FC25 Kalia, S., P062 Kamstrup, M., FC01 Kaneko, S., P030 Kapur, N., P078 Karle, A., P024 Kawakami, H., P096 Keermann, M., P097 Kelsell, D., FC14 Kemény, L., P114, P115 Kerbusch, T., P004, P011 van de Kerkhof, P., P022, P083, P094 Keszegpal, A., P009, P089 Khettab, H., FC20 Khoury, L., P117 Kieras, E., P088 Kievit, W., P093 Kimball, A., P004, P091 , P103, P105 Kingo, K., FC10, P097 Kirby, B., P029, P051 Kirkham, B., P034 Kivelevitch, D., P018 Klekotka, P., FC31

Kleyn, E., FC21 , P051, P078 Klijn, S., P093 Kluwig, D., P049, P118 Kofoed, K., P074, P121 Kok, M.R., FC27 Kõks, S., FC10, P097 Kolbinger, F., P024 Kolios, A., FC22 van der Kolk, A., P093 Kölli, C., FC33 Körber, A., FC10, FC26 Korge, B., P017 Korom, I., P115 Koscielny, V., FC21 Kreppel, S., P051 van der Krieken, D., FC04 Krishnasamy, S., P062 Krueger, G., FC12 , P062 Krueger, J., FC08, P013, P088 Krupashankar, D.S., P090 Kubanov, A., P026 Kulkarni, P., P011 Kunder, G.G., P069 Kunjravia, N., P013 Kunze, A., FC11 Kurras, S., P116 Kusumawardani, A., P035

Lacombe, A., P085 Lacour, J.-P., FC29, P032 Lambert, J., P059, P070, P070 Lambert, S., FC16 Landeck, L., P072 Landén, N.X., FC19, P005 Lange-Asschenfeld, B., P079 Langhol ff , W., P055, P062 Langley, R., FC29, P062 Lapointe, A.-K., FC18 Lättekivi, F., P097 Latzko, A., P009 Laws, P., P009, P089 Lazaridou, E., P031 Lebwohl, M., FC32 Lee, J., P088 Leonardi, C., FC29, P022, P085 Leong, A., P036 Leslie, S., P038 Lewczuk, A., P119 Li, C., P050 Li, H., FC12 Li, J., FC31 Li, K., FC08 Li, Q., P004 Li, S., P054, P105 Li, W., P072 Li, X., P013 Liang, J., P050 Liang, Y., FC25 Liao, W., P038 Lichem, R., FC33 Limbu, L., P001 Liu, X., P106 Lockshin, B., P016 Lockwood, S., P091 Loft, N.D., P074 Löhr, S., FC10 Lovato, P., P099 Lu, C., P006



from gene to clinic

135

Author Index 3

© 2017 The AuthorsBJD © 2017 British Association of Dermatologists British Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4

Luan, C., P073 Lubberts, E., FC27, P063, P064, P065 Luger, T., P085 van Lüimig, P., P083 Lunt, M., P051, P052, P086 Lüscher, B., P049, P118

Maa, J.-F., P029 McCarthy, S., FC12 McElhone, K., P051, P052 McGovern, A., FC15 Macleod, T., P009 Macluskie, G., FC22 Mahé, E., P032 Mahil, S., P034 Mai, S., P077 Maillère, B., P024 Mallbris, L., P014 Man, X.-Y., P072 Manasterski, M., P017 Manmath, P., P085 Manolson, M.F., P058 Mansouri, S., P076 Marini, J.C., P054 Marquardt, Y., P049, P118 Martin, P., FC15 Martini, E., FC19 Maruthappu, T., FC14, P034 Maryam, D., P037 Mashaly, H., P060 Mason, K.J., P051, P052 Matsumoto, Y., P096 Max, N., P120 Mayer, G., P079 Mazur, R., P085 Medeiros, A., P059 Mehta, N., P022 Meisgen, F., P005 Menter, A., FC31, P018 Mentz, H., P017 Mercieca, L., P110 Mesman, R., FC04 Meziane, M., P077 Milliken, M., FC12 Milutinovic, M., P022, P085 Min, M., P072 Mira, D.A., P035 Misery, L., P032 Mlynek, A., FC33 Modiano, P., P032 Møller, T., P117 Montgomery, D., P004 Morita, E., P030 Morrison, P., P116, P122 Moskot, M., P023, P119 Mössner, R., FC10 Motyer, A., P038 Mrowietz, U., FC26, P021, P116, P120, P122 Müllegger, R., FC33 Munoz, E.J., P106 Murphy, G., FC11 Murphy, R., P086 Mus, A.M.C., FC27 Mylonas, A., FC18

Nagy, N., P115 Nair, R., FC04, FC16 , P038

Navarini, A., FC18, P044 Niehues, H., FC04 Nielsen, J., FC28 Nielsen, T.E.T., P100 van Niftrik, L., FC04 Norsgaard, H., P099 Núnez Gómez, N., P017 Nylén, S., FC19

O’Connor, P., P039 O’Donnell, M., P003 Oehrl, S., FC11 Oguro, H., P030 Oji, V., FC10, P120 Oksenberg, J., P038 Okubo, Y., P096 Onsun, N., P041, P042 Oon, H.H., P033 Oortveld, M., FC04 Ormerod, A., P086 Osland, J.M., P073 Otten, M., P044 Otten-Mus, A.-M., P063, P064, P065 Ottosen, M.B., P075 Overton, J., FC12 Ozarmagan, G., P041, P042 Özcan, A., FC22 Ozkaya, D.B., P041, P042

Page, K., P088 Painsi, C., FC33, P079 Palmer, C., P038 Panicker, V.K., P019 Papanastasiou, P., P022 Papp, K., FC29, FC31, P014, P103, P104,

P105 Parasramani, S.G., P069 Parekh, M., P090 Pariser, D., FC29 Parisi, R., P078 Parneix, A., P021 Pascal, C., P085 Pasquali, L., P005 Pastorino, R., P040 Patel, D., FC31 Paul, C., P032, P094 Pawar, D., P090 Pawar, D.R., P069 Peeva, E., P088 Peña, L., P081 Peñaranda, E., P081 Peng, Q., P111 Peterson, L., FC32 Pfa ff , C., P049, P118 Philipp, S., FC10, FC29 Phung, M., P080, P108, P109 Pivarcsi, A., P005 Polzer, P., P104 Ponholzer, P., FC33 Ponnambalam, S., P089 Porter, M., P091 Prasada, R., P019 Praveen, K., FC12 Prens, E., FC27, P063 Price, L., P043, P045, P046 Prinz, J., FC05 Prinz, J.C., FC10, FC17, P066

Puig, L., P092

Quehenberger, F., FC33

Raap, J., P008 Rachida, &.S.-B., P037 Radhakrishnan, K., P019 Radiono, Suradi., P035 Radtke, M., FC21, FC26, FC30 , P044 Rahimi, R., P018 Rajagopalan, M., P003 Ralph, K., FC26 Randazzo, B., P054, P103 Rasmussen, M., P075, P121 Ratzinger, G., FC33 Ray-Jones, H., FC15 van den Reek, J., P083, P093 Reeves, E., FC17 Regnault, P., P021, P026 Régnier, S., P032 Reich, K., FC10, FC26, FC30, FC31, FC32,

P004, P017, P021, P022, P094, P103 Reid, D., P009 Reid, J., FC12 Reimann, E., P097 Rendon, A., FC11 Reynolds, N., P051, P086 Richard, M.-A., P032 Richter, L., FC33 Rigopoulos, D., P055 Riviere, J., P087 Roa, E., P081 Robinson, J., P043, P045, P046 Rodijk-Olthuis, D., FC04 Rolleri, R., FC32 Romiti, R., P003 Roussaki-Schulze, A., P055 Rundquist, I., P113 Rüter, P., P007 Ruzicka, T., P066

Sérézal, I.G., FC19 Salmhofer, W., FC33 Sarkar, M., FC25 Sator, P., FC33 Saxinger, W., FC33 Sayag, M., P087 Sbidian, E., P032 Schäkel, K., FC11 Schafer, P., P016 Schäkel, K., FC10 Schalkwijk, J., FC04 Schalkwijk, L., P083 Scherer, J., FC29 Schill, T., FC10 Schmidbauer, U., P079 Schmutz, J.-L., P032 Schork, N.J., P111 Schulz, P., FC10 Schütz-Bergmayr, M., FC33 Schwichtenberg, U., P017 Segaert, S., P070 Servín, O.R., P029 Seyger, M., P083 Shaker, O., P060 Shear, N.H., P056, P057 Shedden, K., FC06

AUTHOR INDEX

4 Author Index

© 2017 The AuthorsBritish Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4 BJD © 2017 British Association of Dermatologists

Shen, Y.-K., P053, P054, P103, P105 Shi, Y., P025 Singer, J.M., P013 Skak-Nielsen, T., P099 Skov, L., FC01, P074, P075, P100, P117, P121 Smith, C., FC24, P034, P052, P086 Smolinska, E., P023, P119 Sodha, M., P003 Soltani-Arabshahi, R., P062 Song, M., P053, P103 Sonkoly, E., P005 Sotiriou, E., P031 Souad, S., P037 Soura, E., P055 Spindeldreher, S., P024 Spuls, P., P059 Srivastava, A., P005 Srivastava, B., P062 Stacey, M., P009, P089 Ståhle, M., FC21, P005, P062 Ständer, H., FC10 Ständer, S., P120 Standish, K.A., P111 Steinz, K., FC10 Sticherling, M., FC10, P007, P008 Sticht, H., FC10 Stölzl, D., P116 Strober, B., P016 Strohal, R., FC33 Stuart, P., FC04 Suarez-Farinas, M., P088 Suhrkamp, I., P122 Sullivan, J., P020, P026 Summer, B., P066 Sun, L., P111 Suresh, S.H., P069 Swaroop, H.S., P090 Swindell, W., FC25 Széll, M., FC24, P114 , P115

Talamonti, M., P040 Tan, E., FC24 Tatarski, R., FC33 Tenon, M., P024 Thaçi, D., FC26, P085 Thomas, P., P066 Thompson, E.H.Z., FC29 Thorneloe, R., P101, P123 Thyssen, J., FC01 Tockova, O., P112

Tong, Y., P025 Torz, K., P120 Toth, D., P085 Trautinger, F., FC33 Tsagareishvili, K., P107 Tsai, T.-F., P022 Tsakok, T., FC02 Tsoi, L., FC04, FC25 , P038 Tsuboi, R., P096 Tubach, F., P032 Tuttle, J., FC31 Twelves, S., FC24 Tyring, S., FC29

Uebe, S., FC10

Van Gele, M., P059 Varga, E., P115 VataKuti, S., P011 Velangi, S., P036 Vendelbo, M.H., FC28 Verhaegh, D., FC27 Verma, D., P098 Verma, M., P036 Vernez, M., FC18 Viguier, M., FC20, P032 Virassamynaik, S., P087 Vis, M., P064, P065 van Vlijmen-Willems, I., FC04 Vollmer, S., FC05, FC17, P066 Voorhees, J., FC25 Vukcevic, D., P038 Vural, S., FC05

Wachter, E.A., P013 Wada, R., P011 Walsh, J., FC12 Walsh, S., P056, P057 Walton, S., P086 Wang, H., P111 Wang, P., P072 Wang, W.-H., P027 Wang, X., P025 Wang, Y., P025 Wang, Z., P068, P111 Ward, N., FC25 Warren, R.B., FC15, FC23, P003, P051, P052,

P086, P110 Was fi , Y., P053, P054, P103, P105 Webb, R.T., P078

Weger, W., FC33 Weimar, I., P047 Wenning, L., P011 Wenzel, J., P009 van de Wetering, G., P093 Willaert, F., P070 Williams, R., FC23 Wilsmann-Theis, D., FC10 Wilson, J., P020 Wimmer, J., P044 Winther, S., P102 Wittmann, M., P009, P089 Wolf, P., FC33, P079 Wu, J.J., FC29

Xi, L., P088 Xia, S., P085 Xiao, F., P111 Xing, X., FC25 Xu, H., P025 Xu, J., P095 Xu, W., P014 Xu, X., P063, P064, P065 Xu, Z., P068

Yan, K., P095 Yang, S., P111 Yeung, J., P056, P057, P080, P108, P109 Yin, X., P111 Yiu, Z., P052, P086 You, R., P021, P022, P026 You, Y., P053 Yu, Q., P025 Yuan, R., P073

Zachariae, C., FC01, P074, P100, P117, P121 Zeeuwen, P., FC04 Zhang, B., P088 Zhang, C.-L., P027 Zhang, L., P104 Zhang, W., P088 Zhang, X., FC13, P025, P050, P095, P111 Zheng, M., P072 Zheng, X., P111 Zhou, H., P054 Zhu, Y., P054 Zopf, Y., P007 Zorko, M.S., P112 Zuo, X., P111


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