cost-efficacy of biologic therapies for moderate to severe psoriasis from the perspective of the...

Pharmacology and therapeutics

Cost-efficacy of biologic therapies for moderate to severe

psoriasis from the perspective of the Taiwanese healthcare

system

Shu-Hui Wang1,2,3, MD, MS, Ching-Chi Chi4,5, MD, MMS, DPhil (Oxf), andSindy Hu3,5,6, MD, MS

1Department of Dermatology, Far Eastern

Memorial Hospital, New Taipei,2Department of Healthcare Administration,

Oriental Institute of Technology, New

Taipei, 3Department of Cosmetic Science,

Chang Gung University of Science and

Technology, Taoyuan, 4Department of

Dermatology, Chang Gung Memorial

Hospital Chiayi, Chiayi, 5College of

Medicine, Chang Gung University,

Taoyuan, and 6Department of Dermatology,

Chang Gung Memorial Hospital Taoyuan,

Taoyuan, Taiwan

Correspondence

Ching-Chi Chi, MD, MMS, DPhil

Department of Dermatology

Chang Gung Memorial Hospital, Chiayi

6, Section West, Chia-Pu Road

Puzih, Chiayi 61363, Taiwan

E-mails: [email protected];

[email protected]

Conflicts of interest: None.

Abstract

Background Biologic therapies are more effective than conventional therapies in the

treatment of psoriasis, but they are also more costly.

Objectives The aim of this study was to compare the cost-efficacy of etanercept,

adalimumab, and ustekinumab therapies in the treatment of moderate to severe psoriasis

in a Taiwanese setting.

Methods We conducted a meta-analysis of randomized, placebo-controlled trials to

calculate the incremental efficacy of etanercept, adalimumab, and ustekinumab,

respectively, in affecting a reduction of ≥75% in score on the Psoriasis Area and Severity

Index (PASI 75). The base, best case, and worst case incremental cost-effectiveness

ratios (ICERs) for one subject to achieve PASI 75 were calculated for the purposes of

economic analysis.

Results One-year ICERs per PASI 75 responder were US$ 39,709 (best scenario US$

36,400; worst scenario US$ 43,680), US$ 23,711 (best scenario US$ 22,633; worst

scenario US$ 25,319), and US$ 26,329 (best scenario US$ 24,780; worst scenario US$

27,623) for etanercept, adalimumab, and ustekinumab, respectively. Two year ICERs per

PASI 75 responder were US$ 71,973 (best scenario US$ 65,975; worst scenario US$

79,170), US$ 62,665 (best scenario US$ 59,817; worst scenario US$ 66,914), and US$

52,657 (best scenario US$ 49,560; worst scenario US$ 55,427) for etanercept,

adalimumab, and ustekinumab, respectively.

Conclusions In a Taiwanese setting, adalimumab and ustekinumab had lower 1-year

costs per PASI 75 responder than etanercept, and ustekinumab had the lowest 2-year cost

per PASI 75 responder.

Introduction

Psoriasis is a chronic inflammatory dermatosis affecting0.23% of the Taiwanese population1,2 or around 53,000Taiwanese individuals. Approximately 14–17% of psoria-tic patients have moderate to severe disease that requirestreatment with systemic therapies or phototherapy.1,2

People with psoriasis, especially those with moderate tosevere psoriasis, have an increased risk for comorbiditiesincluding hypertension, diabetes, hyperlipidemia, andheart disease.1,2

Three biologic therapies for treating moderate to severepsoriasis (etanercept, adalimumab, and ustekinumab)have been approved for reimbursement by Taiwan'sBureau of National Health Insurance (BNHI).3 Etaner-cept and adalimumab bind and neutralize tumor necrosisfactor (TNF),4,5 whereas ustekinumab is a monoclonal

antibody that blocks interleukin-12 and interleukin-23,which are involved in inflammation and immuneresponse.6

Patients with moderate to severe psoriasis (defined by aPsoriasis Area and Severity Index [PASI] score of ≥10) areeligible for reimbursement if the psoriasis has notresponded to regular phototherapy and at least twosystemic agents (such as acitretin, methotrexate, andcyclosporine) or if the patient is intolerant of or has acontraindication for these treatments. Before initiatingbiologic therapy, the dermatologist must obtain pre-approval from the BNHI. After examining the applicationand confirming the patient's eligibility, the BNHI willapprove six months of biologic treatment. Dermatologistsare required to follow-up the clinical response and mayapply for a 6-month extension treatment when this isindicated.3

ª 2014 The International Society of Dermatology International Journal of Dermatology 2014, 53, 1151–1156

1151

Over the past few years, healthcare expenditure hasincreased as the baby boomer generation has aged and asa result of the introduction of expensive novel healthtechnology. It is therefore important to efficiently allocatethe limited resources available for treating chronic dis-eases such as psoriasis.7 Compared with conventionaltherapies, biologic therapies are more effective in treatingpsoriasis, but they are also more expensive. The objectiveof this study was to compare the cost efficacy of biologictherapies in the treatment of moderate to severe psoriasisin a Taiwanese setting.

Materials and methods

Meta-analysis

A meta-analysis of randomized, placebo-controlled trials was

conducted to determine the efficacy of biologic therapies in

treating psoriasis. The Cochrane Central Register of Controlled

Trials and MEDLINE were searched for relevant trials from the

inception of the respective databases to October 2012.

Inclusion criteria required that studies referred to randomized,

placebo-controlled trials on the efficacy of etanercept,

adalimumab, or ustekinumab therapies for moderate to severe

psoriasis in adults who adhered to the approved regimens. The

approved regimen for etanercept comprised doses of 50 mg

twice weekly for 12 weeks, followed by 25 mg twice weekly or

50 mg once weekly. The approved weight-based regimen for

adalimumab is 80 mg at week 0 followed by 40 mg every other

week. The approved regimen for ustekinumab is 45 mg at

weeks 0 and 4, followed by 45 mg every 12 weeks.3 Trials that

did not adhere to an approved regimen were excluded. If a trial

included an arm using an approved regimen and another arm

using an unapproved regimen, we extracted data from the

approved regimen and placebo arms only. Although a double

dose of ustekinumab (i.e. 90 mg at weeks 0 and 4, followed by

90 mg every 12 weeks) is recommended for patients weighing

>100 kg,6 Taiwan's BNHI does not reimburse this regimen.

Therefore, we considered only the ustekinumab 45 mg regimen

in this meta-analysis.

The efficacy outcome was the proportion of participants

achieving a reduction of ≥75% in PASI score (PASI 75) at the

end of the placebo-controlled period. We calculated the

incremental efficacy (IE) of each biologic therapy according to

the gain in the proportion of participants achieving PASI 75

after biologic treatment compared with those on placebo

treatment (IE represents the proportion of participants achieving

PASI 75 in the biologics group minus the proportion of

participants achieving PASI 75 in the placebo group).

We used intention-to-treat (ITT) analysis to calculate the

proportion of participants achieving PASI 75 based on all

randomized participants. All randomized participants for whom

data on PASI 75 were missing were considered to represent

treatment failures. We conducted a meta-analysis to obtain the

IE and 95% confidence interval (CI) using the Mantel–Haenszel

method.8 Review Manager Version 5.1 (Nordic Cochrane

Centre, Cochrane Collaboration, Copenhagen, Denmark) was

used for meta-analysis.

Cost-efficacy analysis

For the cost-efficacy analysis, we considered the direct costs of

reimbursement for drugs dispensed according to the approved

regimens. Taiwan's BNHI reimburses biologics at a fixed price

which is subject to adjustment every several years. Therefore,

the reimbursed drug price is very constant. We used the cost of

reimbursement in effect in February 2013 for the present

study.9

We compared the incremental cost-effectiveness ratios

(ICERs) of the biologic therapies. The ICER represents the ratio

of the increase in costs to the therapy's IE ([cost of

biologic � cost of placebo]/[proportion of participants achieving

PASI 75 in the biologic group–proportion of participants

achieving PASI 75 in the placebo group]). The costs of placebo

were assumed to be nil. The ICER represents the incremental

cost for one subject to achieve PASI 75. A biologic therapy is

more cost-effective if it has a lower ICER. We calculated 1-year

(52-week) and 2-year (104-week) base case ICERs per

participant achieving PASI 75.

In addition to the base case ICER derived from the IE, worst

and best scenario ICERs were calculated based on,

respectively, the lower and upper 95% confidence limits of the

IE. The range between the worst and best scenario ICERs can

be regarded as the 95% CI of the ICER and was used to

compare the ICERs of different biologic therapies.

Results

Incremental efficacy

A total of 1430 records were identified by searching thedatabases. Two additional records were obtained from apharmaceutical company. After filtering the studies toremove duplicates and exclude those that did not useapproved regimens, lacked a placebo group, or did notreport relevant outcomes, 13 trials were included in themeta-analysis.10–22 All of the included trials were foundto be of high quality when appraised using the CochraneCollaboration's tool for assessing risk for bias in random-ized trials and were of low heterogeneity.8 The efficacyoutcomes of the 13 trials are summarized in Table 1.A meta-analysis (Fig. 1) showed the IEs to PASI 75 to

be 44% (95% CI 40–48%), 63% (95% CI 59–66%), and64% (95% CI 61–68%) for etanercept, adalimumab, andustekinumab, respectively.

Cost-efficacy

As Table 2 shows, both adalimumab and ustekinumabhad favorable 1-year ICERs (ICER of adalimumab: US$

International Journal of Dermatology 2014, 53, 1151–1156 ª 2014 The International Society of Dermatology

Pharmacology and therapeutics Cost-efficacy of biologics for psoriasis Wang et al.1152

23,711 in the base case, US$ 22,633 in the best scenario,US$ 25,319 in the worst scenario; ICER of ustekinumab45 mg: US$ 26,329 in the base case, US$ 24,780 in thebest scenario, US$ 27,623 in the worst scenario). Etaner-cept had a higher ICER of US$ 39,709 in the base case,US$ 36,400 in the best scenario, and US$ 43,680 in theworst scenario.Ustekinumab had the most favorable 2-year ICER (US$

52,657 in the base case, US$ 49,560 in the best scenario,US$ 55,247 in the worst scenario), followed by ada-limumab (US$ 62,665 in the base case, US$ 59,817 in thebest scenario, US$ 66,914 in the worst scenario). The2-year ICER of etanercept was US$ 71,973 in the basecase, US$ 65,975 in the best scenario, and US$ 79,170 inthe worst scenario.

Discussion

The present study represents the first economic analysisof the efficacy of biologic therapies in moderate to severepsoriasis in a Taiwanese setting. This study found that

adalimumab and ustekinumab had lower 1-year costs perPASI 75 responder, and ustekinumab had the lowest2-year cost per PASI 75 responder. Etanercept had highercosts per PASI 75 responder.The ITT approach is considered the best way to assess

treatment efficacy because it maintains prognostic balancegenerated by the original randomization and best mimicsactual practice, in which patients may drop out or switchtreatments.8 A few of the trials included did not use theITT approach,10–12,14 and several previous economicanalyses on the use of biologic therapies for psoriasis alsohave not used the ITT approach to obtain efficacy esti-mates.23–25 The present study used the ITT approach torecalculate outcome data and thus provides less biasedcost-efficacy estimates.The present economic analysis was based on PASI 75

response at the end of the induction phase of the biologictherapy (weeks 12–16), which is a widely used treatmentgoal and is applied in many clinical trials as a primaryendpoint.26 The efficacy of biologics may change withtime. However, for ethical reasons, placebo-treated

Table 1 Efficacy outcome data reported in the included trials (n = 13)

Trial, authors (year) Intervention

Randomized

participants, n

Timing of outcome

assessment

Participants achieving

PASI 75, n (%)

Etanercept trials

Leonardi et al. (2003)10 Etanercept 168 Week 12 81 (48)

Placebo 168 6 (4)

Papp et al. (2005)11 Etanercept 203 Week 12 94 (46)

Placebo 204 6 (3)

Tyring et al. (2006)12 Etanercept 311 Week 12 147 (47)

Placebo 309 15 (5)

Bagel et al. (2012)13 Etanercept 62 Week 12 37 (59)

Placebo 62 3 (5)

Adalimumab trials

Gordon et al. (2006)14 Adalimumab 46 Week 12 24 (52)

Placebo 52 2 (4)

Menter et al. (2008)15 Adalimumab 814 Week 16 578 (71)

Placebo 398 26 (7)

Saurat et al. (2008)16 Adalimumab 108 Week 16 86 (80)

Placebo 53 10 (19)

Asahina et al. (2010)17 Adalimumab 43 Week 16 27 (63)

Placebo 46 2 (4)

Ustekinumab trials

Papp et al. (2008)19 Ustekinumab 45 mg 409 Week 12 273 (67)

Placebo 410 15 (4)

Leonardi et al. (2008)18 Ustekinumab 45 mg 255 Week 12 171 (67)

Placebo 255 8 (3)

Tsai et al. (2011)20 Ustekinumab 45 mg 61 Week 12 41 (67)

Placebo 60 3 (5)

Igarashi et al. (2012)21 Ustekinumab 45 mg 65 Week 12 38 (58)

Placebo 33 2 (6)

Zheng et al. (2012)22 Ustekinumab 45 mg 160 Week 12 132 (83)

Placebo 162 18 (11)

PASI 75, reduction of ≥75% in score on the Psoriasis Area and Severity Index.


Wang et al. Cost-efficacy of biologics for psoriasis Pharmacology and therapeutics 1153

participants in all clinical trials were switched to activebiologic treatments after weeks 12–16. It is thereforeimpossible to obtain placebo-controlled data on long-termIE. Furthermore, expert consensus and regulating bodieshave advised that the PASI response at the end of theinduction phase should be used to judge whether or notthe treatment goal has been achieved and to assesswhether the treatment should be adjusted.3,26.

The ustekinumab 90 mg regimen is recommended for usein patients weighing >100 kg because it is more effective thanthe ustekinumab 45 mg regimen in such patients.6 Taiwan'sBNHI reimburses only for ustekinumab 45 mg regimens.However, only 5% of participants in the Taiwanese trialweighed >100 kg,20 and the proportion of PASI 75 respond-ers on an ustekinumab 45 mg regimen was found to remainwithin the range of 49–54% in subjects weighing >100 kg.6

Figure 1 Meta-analysis of data reported in 13 trials on a reduction of ≥75% in score on the Psoriasis Area and Severity Index.M-H, Mantel–Haenszel method; 95% CI, 95% confidence interval

Table 2 Incremental cost-effectiveness ratio (ICER) per one participant achieving a reduction of ≥75% in score on the PsoriasisArea and Severity Index

Biologic

1 year ICER, US$ 2 year ICER, US$

Base case Best scenario Worst scenario Base case Best scenario Worst scenario

Etanercept 39 709 36 400 43 680 71 973 65 975 79 170

Adalimumab 23 711 22 633 25 319 62 665 59 817 66 914

Ustekinumab 26 329 24 780 27 623 52 657 49 560 55 247



Concomitant psoriatic arthritis is present in 8–15% ofpeople affected by psoriasis.2,27 In such patients, treat-ment with etanercept and adalimumab is preferablebecause these drugs have additional efficacy in arthritis.4,5

The present economic analysis considered only the clin-ical response of skin lesions, but biologic therapies forpsoriasis have additional benefits in improving quality oflife and emotional well-being. All three biologics havebeen found to improve patients’ quality of life.28–30 Inaddition, etanercept has been found to improve fatigueand depression in line with improvements in joint andskin symptoms.12.

In conclusion, in this Taiwanese setting, the 1-year costsper PASI 75 responder of adalimumab and ustekinumabwere lower than that of etanercept, and ustekinumab hadthe lowest 2-year cost per PASI 75 responder. Thiseconomic analysis may serve as a reference to helpclinicians and healthcare payers to allocate the limitedhealthcare resources available for treating psoriasis in themost efficient way possible.

Acknowledgment

The authors thank Professor Fenella Wojnarowska, Nuf-field Department of Clinical Medicine, University ofOxford, Oxford, UK, for her comments on the manuscript.

References

1 Tsai TF, Wang TS, Hung ST, et al. Epidemiology andcomorbidities of psoriasis patients in a national databasein Taiwan. J Dermatol Sci 2011; 63: 40–46.

2 Chang YT, Chen TJ, Liu PC, et al. Epidemiologicalstudy of psoriasis in the national health insurancedatabase in Taiwan. Acta Derm Venereol 2009; 89:262–266.

3 Bureau of National Health Insurance. Regulations forReimbursed Immunologic Agents for Treating Psoriasis.Taipei: National Health Insurance Administration,Ministry of Health and Welfare, 2012.

4 Immunex Corp. Prescribing Information for Enbrel�.Thousand Oaks, CA: Immunex Corp, 2011.

5 Abbott Laboratories, Inc. Prescribing Information for

Humira�. North Chicago, IL: Abbott Laboratories, Inc.,2012.

6 Janssen Biotech, Inc. Prescribing Information for

Stelara�. Horsham, PA: Janssen Biotech, Inc., 2012.7 Chi CC. Evidence-based dermatology. Dermatologica

Sinica 2013; 31: 2–6.8 Higgins JPT, Green S. Cochrane Handbook for

Systematic Reviews of Interventions. Chichester:Wiley-Blackwell, 2008.

9 Bureau of National Health Insurance. Queries on

Reimbursed Medicines [WWW document]Availablefrom: http://www.nhi.gov.tw/query/query1.aspx?menu=

21&menu_id=713&webdata_id=3510&WD_ID=851.[Accessed September 12, 2012.]

10 Leonardi CL, Powers JL, Matheson RT, et al. Etanerceptas monotherapy in patients with psoriasis. N Engl J Med

2003; 349: 2014–2022.11 Papp KA, Tyring S, Lahfa M, et al. A global phase III

randomized controlled trial of etanercept in psoriasis:safety, efficacy, and effect of dose reduction. Br JDermatol 2005; 152: 1304–1312.

12 Tyring S, Gottlieb A, Papp K, et al. Etanercept andclinical outcomes, fatigue, and depression in psoriasis:double-blind placebo-controlled randomized phase IIItrial. Lancet 2006; 367: 29–35.

13 Bagel J, Lynde C, Tyring S, et al. Moderate to severeplaque psoriasis with scalp involvement: a randomized,double-blind, placebo-controlled study of etanercept. JAm Acad Dermatol 2012; 67: 86–92.

14 Gordon KB, Langley RG, Leonardi C, et al. Clinicalresponse to adalimumab treatment in patients withmoderate to severe psoriasis: double-blind, randomizedcontrolled trial and open-label extension study. J AmAcad Dermatol 2006; 55: 598–606.

15 Menter A, Tyring SK, Gordon K, et al. Adalimumab therapyfor moderate to severe psoriasis: a randomized, controlledphase III trial. J Am Acad Dermatol 2008; 58: 106–115.

16 Saurat JH, Stingl G, Dubertret L, et al. Efficacy andsafety results from the randomized controlledcomparative study of adalimumab vs. methotrexate vs.placebo in patients with psoriasis (CHAMPION). Br JDermatol 2008; 158: 558–566.

17 Asahina A, Nakagawa H, Etoh T, et al. Adalimumab inJapanese patients with moderate to severe chronic plaquepsoriasis: efficacy and safety results from a Phase II/IIIrandomized controlled study. J Dermatol 2010; 37: 299–310.

18 Leonardi CL, Kimball AB, Papp KA, et al. Efficacy andsafety of ustekinumab, a human interleukin-12/23monoclonal antibody, in patients with psoriasis: 76-weekresults from a randomized, double-blind,placebo-controlled trial (PHOENIX 1). Lancet 2008;371: 1665–1674.

19 Papp KA, Langley RG, Lebwohl M, et al. Efficacy andsafety of ustekinumab, a human interleukin-12/23monoclonal antibody, in patients with psoriasis: 52-weekresults from a randomized, double-blind,placebo-controlled trial (PHOENIX 2). Lancet 2008;371: 1675–1684.

20 Tsai TF, Ho JC, Song M, et al. Efficacy and safety ofustekinumab for the treatment of moderate-to-severepsoriasis: a phase III, randomized, placebo-controlledtrial in Taiwanese and Korean patients (PEARL). JDermatol Sci 2011; 63: 154–163.

21 Igarashi A, Kato T, Kato M, et al. Japanese UstekinumabStudy. Efficacy and safety of ustekinumab in Japanesepatients with moderate-to-severe plaque-type psoriasis:longterm results from a phase II/III clinical trial. JDermatol 2012; 39: 242–252.


Wang et al. Cost-efficacy of biologics for psoriasis Pharmacology and therapeutics 1155

22 Zheng M, Zhu XT, Song M, et al. A randomized,double-blind, placebo-controlled study of ustekinumab inChinese patients with moderate to severe plaquepsoriasis: LOTUS trial results. J Dermatol 2012; 39:238–239.

23 Nelson AA, Pearce DJ, Fleischer AB Jr, et al.Cost-effectiveness of biologic treatments for psoriasisbased on subjective and objective efficacy measuresassessed over a 12-week treatment period. J Am Acad

Dermatol 2008; 58: 125–135.24 Ferrandiz C, Garcia A, Blasco AJ, et al. Cost-efficacy of

adalimumab, etanercept, infliximab and ustekinumab formoderate-to-severe plaque psoriasis. J Eur AcadDermatol Venereol 2012; 26: 768–777.

25 Igarashi A, Kuwabara H, Fahrbach K, et al. Cost-efficacycomparison of biological therapies for patients withmoderate to severe psoriasis in Japan. J Dermatolog

Treat 2013; 24: 351–355.26 Mrowietz U, Kragballe K, Reich K, et al. Definition of

treatment goals for moderate to severe psoriasis: a

European consensus. Arch Dermatol Res 2011; 303:1–10.

27 Winchester R. Psoriatic arthritis. In: Wolff K, GoldsmithLA, Katz SI, et al., eds. Fitzpatrick's Dermatology in

General Medicine, 7th edn. New York, NY: McGrawHill, 2008: 194–207.

28 Krueger GG, Langley RG, Finlay AY, et al.Patient-reported outcomes of psoriasis improvement withetanercept therapy: results of a randomized phase IIItrial. Br J Dermatol 2005; 153: 1192–1199.

29 Revicki D, Willian MK, Saurat JH, et al. Impact ofadalimumab treatment on health-related quality of lifeand other patient-reported outcomes: results from a16-week randomized controlled trial in patients withmoderate to severe plaque psoriasis. Br J Dermatol 2008;158: 549–557.

30 Lebwohl M, Papp K, Han C, et al. Ustekinumab improveshealth-related quality of life in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial. Br JDermatol 2010; 162: 137–146.



cost-efficacy of biologic therapies for moderate to severe psoriasis from the perspective of the...

Documents