Efficacy and Safety of Apremilast in Patients With Moderate Plaque Psoriasis With Lower BSA: Week 16 Results from the UNVEIL Study
August 2017 | Volume 16 | Issue 8 | Original Article | 801 | Copyright © August 2017
Bruce Strober MD PhD,a Jerry Bagel MD,b Mark Lebwohl MD,c Linda Stein Gold MD,d J. Mark Jackson MD,e Rongdean Chen PhD,f* Joana Goncalves MD,f Eugenia Levi PharmD,f and Kristina Callis Duffin MD MSg
aUniversity of Connecticut, Farm ington, CT, and Probity Medical Research, Waterloo, Ontario, Canada bPsoriasis Treatment Center of Central New Jersey, East Windsor, NJ cIcahn School of Medicine at Mount Sinai, New York, NY dHenry Ford Health System, West Bloomfield, MI eUniversity of Louisville, Forefront Dermatology, Louisville, KY fCelgene Corporation, Summit, NJ gUniversity of Utah, Salt Lake City, UT *Employed by Celgene Corporation at the time of study conduct.
pathways relevant to the pathogenesis of psoriasis.10 In the phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM)11,12 program, apremilast was effective and demonstrated acceptable tolerability in patients with moderate to severe plaque psoriasis. Patients in the ESTEEM studies were required to have ≥10% BSA involvement and static Physician’s Global Assessment (sPGA) score ≥3, and were allowed to have received previous systemic therapy, including biologics. The current phase IV multicenter, randomized, placebo-controlled, double-blind study (Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis [UNVEIL]; NCT02425826) was conducted to assess efficacy and safety of apremilast in patients with moderate plaque psoriasis (5% to 10% BSA involvement and sPGA score of 3 [moderate] on a 6-point scale) who were naive to systemic and biologic therapy. UNVEIL is the first randomized, placebo-controlled study to prospectively evaluate the efficacy of a systemic oral therapy exclusively in patients with moderate psoriasis (5% to 10% BSA) using the sPGA and BSA involvement (PGAxBSA) tool. The PGAxBSA tool is a simple alternative for assessing response to therapy that may overcome some limitations of the Psoriasis Area and Severity Index (PASI) with respect to detecting change in disease severity in patients with more moderate disease.13,14 A post hoc analysis of ESTEEM 1 and 2 demonstrated that PGAx-BSA is sensitive to therapeutic response with apremilast.15 We report efficacy and safety of apremilast 30 mg twice daily vs placebo through week 16 in patients with moderate plaque psoriasis (5% to 10% BSA) utilizing the PGAxBSA tool.
Patients were adults ≥18 years of age with a diagnosis of chronic plaque psoriasis for ≥6 months and moderate plaque psoriasis, defined by BSA involvement of 5% to 10% and sPGA score of exactly 3 (moderate) based on a 6-point scale (0 [clear] to 5 [very severe]). Patients had no prior exposure to conventional systemics or biologics for treatment of psoriatic arthritis, psoriasis, or any other indication that could affect assessment of psoriasis. Patients with inflammatory or dermatologic conditions which could confound the ability to interpret study data, including forms of psoriasis other than plaque psoriasis (eg, erythrodermic, guttate inverse, pustular) were excluded.
Study Design and Treatment Regimen
Eligible patients were randomized, using a centralized interactive voice response system, to receive apremilast or placebo (2:1) during weeks 0 to 16 (Figure 1). At week 16, placebo patients were switched to apremilast. All patients continued on apremilast through week 52. The institutional review boards of participating medical centers approved the protocol. Patients provided written informed consent before the conduct of study-related procedures.
The primary efficacy end point was the mean percentage change from baseline in PGAxBSA, which represents the product of sPGA and BSA scores, at week 16. Overall BSA affected by psoriasis is estimated based on the patient’s handprint area (entire palmar surface, including ngers), which equates to