Psoriasis is a chronic multisystem inflammatory disorder withsignificant co-morbidities and also profound physical, emo-

tional and social impact on quality of life. A wide array of treat-ment options are available including topical treatments,phototherapy, traditional systemic therapy and several biologicagents.

Despite these advances an effective long-term treatmentof psoriasis remains a challenge and many patients are dissat-isfied with the management of their disease and perceived lackof effect of their therapy. Adherence to treatment can beimproved by considering individual preferences and includingthem in decision making.1

Psoriasis was traditionally viewed as a disorder affectingonly the skin and in some patients also the joints; however,recent evidence has shifted our perception and understand-ing of psoriasis to a more complex inflammatory disease.Patients with severe psoriasis have an increased risk of car-diovascular disease and this inherent risk is probably inde-pendent of conventional cardiovascular risk factors.2 It istherefore of paramount importance that primary-care physi-cians actively screen for and address obesity, hypertension,diabetes and dyslipidaemia in psoriasis patients, many ofwhom are young.3

Another aspect is an overall increased tendency towardsunhealthy behaviour reflected in increased prevalence of smok-ing and alcohol consumption in the psoriatic population, andagain early intervention and counselling are essential.

Finally psoriasis is strongly associated with anxiety anddepression. This relationship is often overlooked and mayplay an important role in further nonadherence to prescribedtreatment.

Topical preparations prescribed by a primary-care physiciancan effectively treat mild to moderate psoriasis. Treatment withtraditional systemic agents or biologics required for moderateto severe psoriasis is initiated in the specialist setting, while

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Psoriasis: current treatment options and recent advancesVeronika Dvorakova MRCPI and Trevor Markham MD, FRCPI

Management of psoriasis is based on a step-wise approach that includes a wide varietyof treatment options. Our Drug reviewfocusses on key points and recent advancesin the management of psoriasis, followedby a review of the prescription data andsources of further information.

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primary-care physicians often participate in ongoing treatmentmonitoring.

Topical therapyTopical corticosteroids

Topical corticosteroids are particularly useful in the treatmentof patients with limited disease, such as on the scalp, palmsand soles. Steroid use is mainly limited by local cutaneous side-effects such as skin atrophy, telangiectasiae, purpura andstriae and also rebound after abrupt discontinuation. Onlylower-strength corticosteroids should be used on the face, flex-ural and genital areas and in children.4

Vitamin D analogues

Vitamin D analogues are effective in the treatment of mild tomoderate psoriasis.5 Local irritation in the form of burning, peel-

ing and pruritus can occur and excessive usage above the rec-ommended dose (100g per week) can lead to hypercalcaemia.Vitamin D analogues can act as a corticosteroid-sparing agentand a combination product containing calcipotriol/betametha-sone (Dovobet) is available.

Coal tar

Coal tar has been used in the treatment of psoriasis for over80 years, often in combination with UV therapy. It is very effec-tive in controlling disease activity in psoriasis and is especiallyindicated for scalp psoriasis, palmoplantar psoriasis andlocalised chronic plaque psoriasis. Coal tar formulations canbe cosmetically less appealing to patients because of the odourand staining of clothes.

Topical calcineurin inhibitors

Tacrolimus6 and pimecrolimus (unlicensed indication) are usedin facial and flexural psoriasis to avoid skin atrophy associatedwith use of topical corticosteroids in these areas.

Dithranol

Dithranol was a principal effective treatment for chronic stableplaque psoriasis for many years. However, skin irritation andstaining have led to its declining use in recent years.

Scalp psoriasisThe scalp area is commonly affected in psoriasis and can bevery difficult to treat. Hair prevents adequate application ofcreams and ointments, and specific formulations such asshampoo, gel, lotion and mousse are often used instead. Scalebuilds up quickly and most treatments must be used on a reg-ular basis. Scalp products usually contain coal tar, topicalsteroids, vitamin D analogues or salicylic acid and their com-binations.

PhototherapyNarrowband UVB

Narrowband UVB (311–313nm) has mainly replaced formerbroadband UVB treatment as it is less erythemogenic, hasshorter clearing times and longer periods of remission.7

Patients usually attend three times per week and narrowbandUVB can also be used in children and pregnant women.

PUVA

PUVA is a combination treatment with psoralen that tem-porarily makes skin more sensitive to subsequent irradiationwith longer-wavelength UVA. Treatment is administered twiceper week. Psoralen tablets can cause nausea and patientsmust also protect skin and eyes from sunlight on treatmentdays. Topical PUVA consists of applying psoralen paintdirectly to the skin or soaking in psoralen solution prior toUVA exposure.

Long-term PUVA therapy is associated with an increasedrisk of squamous cell carcinoma.8 PUVA treatment can there-fore be combined with retinoids or vitamin D analogues in orderto minimise the total dosage of PUVA.

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Figure 2. Ustekinumab is effective in the treatment of chronic plaque psoriasis;efficacy has been shown to be maintained for up to three years

Figure 1. Acitretin, an oral retinoid, is particulary effective in the treatment ofpustular psoriasis

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Targeted phototherapy

Targeted phototherapy with an excimer laser emitting a wave-length of 308nm has been found to be safe and effective in anearly multicentre study9 and efficacy was also demonstratedfor scalp10 and palmoplantar psoriasis.11 Therapy is deliveredby a handheld device directed at the affected areas and risksto uninvolved skin are therefore limited.

Traditional systemic therapyMethotrexate

Methotrexate is an antimetabolite that has been used in thetreatment of psoriasis for many decades and remains one ofthe most effective as well as relatively low-cost therapies.Methotrexate is usually given as a single weekly oral dose andfolic acid supplementation is used to reduce nausea and pre-vent bone marrow toxicity.

Methotrexate use is associated with liver toxicity and regu-lar liver function tests and serial serum procollagen III levelsare used for monitoring therapy.4 Patients with pre-existing con-ditions including obesity, diabetes and alcohol use are at ahigher risk for liver toxicity.12

Ciclosporin

Ciclosporin is an immunosuppressive agent originally devel-oped as an organ transplantation drug in the early 1970s andits efficacy in psoriasis was described shortly thereafter. It actsrapidly and it is excellent for short-term use due to its weakmyelosuppressive effect. Long-term therapy is, however, limitedby an increased risk of hypertension and nephrotoxicity.

Oral retinoids

Oral retinoids are particularly effective in pustular psoriasis(see Figure 1) but are also used for erythrodermic psoriasisand as a maintenance therapy in chronic plaque psoriasis.

Acitretin is prescribed as a single or divided dose of 10–50mg per day, although lower doses of up to 25mg daily areusually used to minimise mucocutaneous side-effects.4

Adverse effects include xerosis, pruritus, cheilitis, alopecia, drymouth, hypertriglyceridaemia, abnormal liver function testsand teratogenicity.

Acitretin cannot be given to women of child-bearing poten-tial who may become pregnant within three years after discon-tinuation of treatment.

Fumaric acid esters

Fumaric acid esters (unlicensed indication) are currently usedfor psoriasis mainly in German-speaking countries and have agood and sustained clinical efficacy.13 Side-effects are com-mon, including lymphopenia, gastrointestinal symptoms andflushing, but can be prevented or reduced by starting at a lowerdose initially with gradual escalation.

BiologicsBiologics are immunomodulators that target specific compo-nents in the molecular pathogenesis of psoriasis. Unlike tradi-tional systemic agents that suppress the entire immune

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system, they specifically interfere with T-cell function andcytokine activity related to psoriasis.

TNF antagonists

Tumour necrosis factor (TNF) alpha is a proinflammatorycytokine that plays an important role in the pathogenesis ofpsoriasis and psoriatic arthritis. There are currently threeapproved agents that target TNF: adalimumab (Humira) andinfliximab (Remicade) are monoclonal antibodies that target

TNF-alpha and etanercept (Enbrel) is a soluble TNF-alpha recep-tor fusion protein.

The National Institute for Health and Care Excellence (NICE)recommends that patients being considered for treatment withbiologics should have severe disease defined by a total psori-asis area and severity index (PASI) score of 10 or more (20 forinfliximab) and also be ineligible for phototherapy or traditionalsystemic treatment due to contraindications, intolerance orprevious treatment failure.4

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Figure 3. Recommended stepwise management of psoriasis (BSA = body surface area)

Localised or mild-to-moderate psoriasis (10–15% BSA)

Trunk and limbs Face, flexures and genitalia Scalp

3rd lineEtanerceptInfliximab

UstekinumabAdalimumab

If above measures fail, refer for dermatological opinion

Widespread or moderate-to-severe psoriasis (15–20% BSA)

EmollientsMild-to-moderate potency topical corticosteroid

Vitamin D cream may be usedwith caution to the hairline and

in flexures

Mild: tar shampooModerate: corticosteroid or calcipotriol scalp lotion or gelSevere: coal tar/salicylicacid/coconut oil ointment

2nd linenUVB/PUVAMethotrexateCiclosporinAcitretin

Fumaric acid esters

1st line Topical treatment as above+/- dermatological referral

EmollientsVitamin D analogue

RetinoidCoal-tar preparation

Corticosteroid ointment/creamDithranol incremental strength,

short contact

Possible psoriasisExclude other disorders – eczema, lichen planus, pityriasis rosea, tinea corporis,

mycosis fungoides, cutaneous lupus erythematosus – and assess degree of psychoso-cial disability due to psoriasis

Adalimumab is a fully human anti-TNF-alpha monoclonalantibody that induces a rapid response with maximum effectachieved between week 12 and 16. Given as a fortnightly injec-tion, adalimumab has shown to maintain efficacy for up tothree years.14

Etanercept is a recombinant human TNF-alpha receptorfusion protein licensed for use in moderate to severe psoriasisat 50mg subcutaneously twice weekly for the first three monthsfollowed by 50mg weekly thereafter.

Infliximab is a chimeric anti-TNF antibody with a rapid onsetof action. Therapy is initiated at 5mg per kg at weeks 0, 2 and6 and then every eight weeks. Loss of efficacy correlates withdevelopment of antibodies, which might be prevented by a com-bined therapy with methotrexate.15

Side-effects Potential side-effects of TNF antagonistsinclude infections, reactivation of tuberculosis and hepatitisB, development of demyelinating disease and drug-inducedlupus.

To assess the long-term safety of biologics the BritishAssociation of Dermatology Biologic Interventions Register(BAD-BIR) has been established. This web-based registercompares adult patients with psoriasis treated with biologics versus patients treated with traditional systemictherapies.16

Interleukin antagonists

Ustekinumab (Stelara) is a fully human monoclonal antibodythat belongs to a new class of biologics targeting the p40 sub-unit of both interleukin (IL)-12 and -23. These cytokines playa role in the regulation of immune response and T-cell acti-vation in psoriasis. The treatment is initiated with 45mg (or90mg if >100kg) at weeks 0 and 4 and then every 12 weeksthereafter.

Ustekinumab is remarkably effective for treatment ofchronic plaque psoriasis, with its onset of action evident asearly as two weeks (see Figure 2). So far efficacy has beenshown to be maintained for up to three years.17

There is a relative lack of long-term safety data for ustek-inumab but a recent pooled analysis of 3117 patients fromphase 2/3 trials showed that ustekinumab was generally welltolerated for up to four years and rates of serious adverseevents (serious infections, malignancies and major cardiovas-cular events) were consistent with those in the general and pso-riasis populations.18

Future treatments Recent research suggests that the Thelper 17 (Th17) lymphocyte subset, which produce the IL-17A cytokine, play a crucial role in psoriasis pathology andtherapeutic approaches focused on this pathway havebrought forward new drugs currently undergoing phase 2/3studies. These include: brodalumab19 (anti-IL-17 receptormonoclonal antibody), ixekizumab20 (anti-IL-17A monoclonalantibody) and secukinumab21 (anti-IL-17A monoclonal anti-body).

Results from short-term studies are promising but furthertrials are required to determine sustained efficacy and highlightpotential side-effects of these new agents.

ConclusionManagement of psoriasis is based on a stepwise approach thattakes the disease extent and impact on the patient’s quality oflife into account (see Figure 3). Topical agents are mainly usedin mild disease and phototherapy in moderate disease. PUVA,traditional systemic agents and biologics are used for moderateto severe psoriasis.

The emergence of new biologic agents provides valuabletreatment options for patients who have failed or are ineligiblefor traditional systemic treatment or phototherapy.

Patients with psoriasis must be screened for cardiovascularrisk factors including high blood pressure, diabetes, hyperlipi-daemia and obesity.

References1. Schmieder A, et al. J Am Acad Dermatol 2012;67(3):363–72.2. Xu T, et al. Br J Dermatol 2012;167(6):1345–50.3. Parsi KK, et al. J Am Acad Dermatol 2012;67(3):357–62.4. NICE. The assessment and management of psoriasis. CG153. 2012.October 2012.5. Highton A, et al. J Am Acad Dermatol 1995;32:67–72.6. Lebwohl M, et al. J Am Acad Dermatol 2044;51:723–30.7. Green C, et al. Br J Dermatol 1988;119:691–6.8. Stern RS, et al. J Am Acad Dermatol 2012;66(4):553–62.9. Feldman SR, et al. J Am Acad Dermatol 2002;46(6):900–6.10. Morison WL, et al. Photodermatol Photoimmunol Photomed2006;22:181–3.11. Nistico SP, et al. J Eur Acad Dermatol Venereol 2006;20:523–6.12. Kalb RE, et al. J Am Acad Dermatol 2009;60(5):824–37.13. Reich K, et al. JDDG 2009;7:603–11.14. Gordon K, et al. J Am Acad Dermatol 2012;66:241–51.15. Maini RN, et al. Arthritis Rheum 1998;41:1552–63.16. Burden AD, et al. Br J Dermatol 2012;166:545–54.17. Kimball A, et al. Br J Dermatol 2012;166:861–72.18. Reich K, et al. J Drugs Dermatol 2012;11:300–12.19. Papp KA, et al. N Engl J Med 2012;366:1181–9.20. Leonardi C, et al. N Engl J Med 2012;366:119–91. 21. Papp KA, et al. Br J Dermatol 2012;168:412–21.

Declaration of interestsNone to declare.

Dr Dvorakova is a specialist registrar in dermatology and DrMarkham is consultant dermatologist at University HospitalGalway, Ireland

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KEY POINTS

n topical agents (emollients, tar, steroids, vitamin D ana-logues) remain the mainstay of treatment for mild to mod-erate psoriasis

n PUVA, traditional systemic agents and biologics are usedfor moderate to severe disease

n biologics are used for patients who have failed or are ineli-gible for traditional systemic agents or phototherapy

n patients must be screened for cardiovascular risk factors

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Prescription reviewGPs in England wrote 1.2 million scrips for psoriasis prepara-tions in 2012, at a total cost of £48 million. Calcipotriolaccounted for 77 per cent of volume and 90 per cent of spend-ing, of which two-thirds of scrips and 80 per cent of costs werefor Dovobet (calcipotriol/betamethasone) ointment and gel.By contrast, only 18 per cent of scrips were for calcipotriolointment (Dovonex) 50µg per g, amounting to 10 per cent ofspending.

Tar and Cocois (coal tar solution/salicylic acid/sulphur incoconut oil) products were the most frequently prescribed ofthe remaining preparations, at a cost of about £2.1 million.

Use of the retinoids acitretin (for resistant psoriasis) and tazarotene (for mild to moderate psoriasis; Zorac), and the vitamin D analogue tacalcitol (Curatoderm), was rel-atively low.

No. scrips Cost Mean cost (000s) (£000s) per scrip (£)

acitretin 15 641 41.54calcipotriol 922 42 862 46.49calcitriol 30 502 16.58Cocois 93 959 10.29dithranol 15 123 8.00salicylic acid 7 551 78.92Polytar emollient 8 58 6.85tacalcitol 15 435 28.22tars 53 1 138 21.56tazarotene 3 66 22.03

Table 1. Number and cost of prescriptions for psoriasis preparationsin England, 2012

ResourcesFurther readingPsoriasis. Griffiths CEM, et al. In: Burns T, et al, eds. Rook’s text-book of dermatology, 8th ed. Oxford: Wiley-Blackwell,2010;1589–649.

GuidelinesAdalimumab for the treatment of adults with psoriasis. TA146.NICE, June 2008.

]Etanercept and efalizumab for the treatment of adults withpsoriasis. TA103. NICE, July 2006.

Infliximab for the treatment of adults with psoriasis. TA134.NICE, January 2008.

Psoriasis – general management. British Association ofDermatologists, 2008. www.bad.org.uk/site/769/Default.aspx.

Psoriasis – management. NHS Clinical Knowledge Summaries.www.cks.nhs.uk/psoriasis.

The assessment and management of psoriasis. CG153. NICE,October 2012.

Ustekinumab for the treatment of adults with moderate tosevere psoriasis. TA180. NICE, September 2009.

Groups and organisationsBritish Association of Dermatologists. Tel: 0207 383 0266; e-mail: admin@bad.org.uk; website: www.bad.org.uk.

Psoriasis Association. Tel: 0845 676 0076; e-mail: mail@pso-riasis-association.org.uk; website: www.psoriasis-association.org.uk.

Psoriasis and Psoriatic Arthritis Alliance (PAPAA). Tel: 01923672837; e-mail: info@papaa.org; website: www.papaa.org.

Websiteswww.psoriasis.org. This site is provided by the NationalPsoriasis Foundation and gives information about psoriasis ingeneral and also current research into psoriasis and treat-ments.

www.psoriasis-help.org.uk. The Psoriasis Help Organisation sitecontains information about treatments, and also provides a dis-cussion forum for psoriasis sufferers to exchange views andadvice on living with psoriasis.

Keeping up to date with the latest thinking in prescribing and therapeuticscan be a challenge. However, it is a requirement for all health professionalsto maintain their competency through continued professionaldevelopment.

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