Importance of Complete Skin Clearance in Psoriasis as a Treatment Goal: Implications for Patient-Reported Outcomes

May 2020 | Volume 19 | Issue 5 | Original Article | 487 | Copyright © May 2020

Published online April 24, 2020

Andrew Blauvelt , Jashin J. Wu , April Armstrong , Alan Menter , Clive Liu , Abby Jacobson

aOregon Medical Research Center, Portland, OR bDermatology Research and Education Foundation, Irvine, CA cKeck School of Medicine, University of Southern California, Los Angeles, CA dDivision of Dermatology, Baylor Scott & White, Dallas, TX eBellevue Dermatology, Bellevue, WA fOrtho Dermatologics (a division of Bausch Health US, LLC), Bridgewater, NJ

Abstract
Psoriasis is associated with physical, psychological, social, and economic burdens that lead to substantial impairment over a patient’s lifetime. It is important to understand how different skin clearance levels may relate to patient perceptions of psoriasis symptoms and health-related quality of life. Here, we highlight notable advantages to complete skin clearance relative to high levels of efficacy without complete skin clearance, including meaningful improvements in patient-reported signs and symptoms of psoriasis, a higher mean proportion of symptom-free days, and significant improvements in quality of life. We also review biologic therapies associated with high percentages of complete skin clearance and significant improvements in signs and symptoms of psoriasis, notably brodalumab. These therapies are likely to play important roles in the future treatment of moderate-to-severe psoriasis, given that improvement in quality of life is of significant value relative to biologics or other systemic therapies associated with lower rates of complete skin clearance.

J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.4957

INTRODUCTION

Psoriasis affects ~3% of adults in the United States and is associated with significant physical, psychological, social, and economic burdens that result in cumulative impairment over a patient’s lifetime.1,2 Approximately 39% of patients have moderate disease and 36% have severe disease according to a National Psoriasis Foundation biannual survey of >5200 respondents with psoriasis or psoriatic arthritis (2003 through 2011).3 Despite the improvement in outcomes that accompanied the advent of tumor necrosis factor (TNF) α inhibitors in psoriasis treatment 15 years ago, a substantial proportion of patients with moderate-to-severe psoriasis receiving this class of biologic agent or the interleukin-12 (IL-12)/IL-23 inhibitor ustekinumab still do not achieve high skin clearance levels.4,5 In a meta-analysis, only 10.7% to 49.5% of such patients achieved ≥90% improvement from baseline in the psoriasis area and severity index (PASI 90) with a TNFα inhibitor, and 35% to 47.2% achieved PASI 90 with ustekinumab.4 These responses may not meet current expectations, especially because experts recommend that the benchmarks of treatment success should now be PASI 90 or PASI 100.6 Moreover, in a cross-sectional study in real-world settings (n=713), only 34.2% to 47.7% of patients receiving etanercept, ustekinumab, or adalimumab achieved an outcome of “clear” or “almost clear” on the psoriasis global assessment (PGA) measure.5 Evidence also suggests that response to TNFα inhibitors may diminish or cease over time.7,8 In a retrospective real-world analysis, 46.8% of individuals with psoriasis eventually lost response to adalimumab monotherapy, with an average of 541 days before treatment failure.9 Similarly, 75.6% of individuals with severe psoriasis eventually lost response to etanercept over an average of 993 days.10 Notably, patients receiving the anti–IL-17A biologic secukinumab in a real-world setting may also lose response. Of 53 patients receiving secukinumab in the clinic for at least 32 weeks, 10 (18.9%) experienced loss of efficacy despite previously achieving substantial clearance of lesions. Loss of efficacy with secukinumab in these 10 patients occurred with a median onset of 29.4 weeks, and 70% of these patients experienced loss of efficacy at 24 to 32 weeks.11

In an international survey of 8338 patients with psoriasis, 56% of respondents were satisfied with their current therapy, while 20% were dissatisfied and 24% were uncertain if they were satisfied.12 There was a correlation between treatment satisfaction and having clear/almost clear skin.12 In an analysis of 609 Nordic patients from the same study, not achieving clear skin was a primary reason (62%) for treatment dissatisfaction.13 In another study, Egeberg and Thyssen surveyed 7858 patients with psoriasis or atopic dermatitis who expressed a strong interest in complete or near complete skin clearance.14 Several discrete-choice experiments have demonstrated that patients are willing