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The New Psoriasis Paradigm: Striving for Complete Clearance

June 2020 | Volume 19 | Issue 6 | Original Article | 652 | Copyright © June 2020


Published online May 29, 2020

Leon H. Kircik MD

Icahn School of Medicine at Mount Sinai in New York, NY; Indiana Medical Center in Indianapolis, IN; Medical Director of Physicians Skin Care, PLLC; DermResearch, PLLC in Louisville, KY

Abstract
Newer biologics have introduced the possibility of higher and more complete clearance rates than previously possible. For many patients, PASI 90 and PASI 100 responses are realistic. Furthermore, higher levels of clearance, particularly total clearance, is associated with marked improvements in quality of life. Little data is available on the clinical benefits of higher clearance levels and how this might relate to improvements in other comorbidities. Is it time for dermatologists to strive for total clearance for our patients? We will examine the evidence that is available around this important topic.
J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.4975

INTRODUCTION

Psoriasis has a profound impact on the quality of life of its affected patients.1 Disturbing their emotional, social, physical, and financial well being, patients with psoriasis have reported a wide array of challenges, including difficulties in the workplace, exclusion from public facilities, trouble finding jobs, and contemplating suicide.1 With the wave of newer biologics, such as ixekizumab, guselkumab, tildrakizumab-asmn, secukinumab, risankizumab-rzaa, and brodalumab, complete clearance is now a real possibility for patients with moderate to severe psoriasis. The percentages of patients on first generation biologics such as etanercept (100 mg/week), adalimumab, and ustekinumab who have achieved complete clearance is low at 7.3%, 16.7%, and 16.4%, respectively.2 Despite this, with almost 15,000 patients currently on biologic therapy for psoriasis, over half remain on the older biologics [etanercept (n=912), adalimumab (n=5.029), and ustekinumab (n=1,599)] (IQVIA, unpublished data, September 2019).

Patients who achieve 100% clearance, or Psoriasis Area and Severity Index (PASI) 100, are more likely to have improved quality of life scores and a reduction in the signs and symptoms of psoriasis.3 However, a recent study showed that only 39% of physicians and patients agree regarding their level of satisfaction with psoriasis control using current treatment methods.4,5 In fact, 51% of physicians were satisfied with the level of treatment control when their patients were not at all satisfied with the level of control they achieved with treatment.4 This finding indicates that although quality of life data provide encouragement for treating to complete clearance, improvements in quality of life or other patient-reported outcomes have traditionally not been enough for a physician to switch biologic treatments for a patient without clear skin unless the patient is also expressing unhappiness with their treatment results and asking for a change. Many patients may not even be aware that higher levels of clearance are now within reach.

Brodalumab-related Benefits for 100% Clearance
One of the biologics that shows promise for achieving total clearance of patients is brodalumab. After 52 weeks and 108 weeks of treatment, more than 2 out of every 3 patients achieved PASI 100 scores (68% and 69%, respectively).3,6 A study by Strober et al pooled data from 3 phase III clinical trials and compared the results for patients who achieved complete clearance (PASI 100) to those who did not (PASI 75) for patient-centered outcomes like the Psoriasis Symptom Index (PSI), an eight-item patient-reported outcome measure developed by Amgen for their product, etanercept, for assessing the severity of plaque psoriasis symptoms and the Dermatology Life Quality Index (DLQI).3,7

For patients taking brodalumab who were at least 75% clear but less than 100% clear, there was a significant improvement (11%) in 100% symptom-free days; however, those who experienced total clearance were 100% symptom-free for 42% of their days (Figure 1A).3 As measured by DLQI, 55% of patients who were at least 75% clear but less than 100% clear rated their DLQI score as a 0 or 1, indicating that psoriasis did not affect their life, compared to 80% of those who were 100% clear (Figure 1B).3 Sixty-eight percent of patients who were at least 75% clear but less than 100% clear were PSI responders (meaning that their PSI total score ≤8 with each symptom rated as either 0 [not at all severe] or 1 [mild]), but for those who were totally clear 88% were responders (Figure 1C).3 In those who were at least 75% clear but less than 100% clear, 13% achieved a PSI = 0 (psoriasis symptoms not at all severe,) while 45% of those who were