Improvement in scalp and nails with apremilast in patients with moderate plaque psoriasis naive to systemic and biologic therapy: 52-week results of the UNVEIL study.

Improvement in scalp and nails with apremilast in patients with moderate plaque psoriasis naive to systemic and biologic therapy: 52-week results of the UNVEIL study.

Presenters: Jackson JM¹, Alikhan A², Lebwohl M³, Stein Gold L⁴, Levi E⁵, Bagel J⁶,

Affiliations: ¹University of Louisville, Forefront Dermatology, Louisville, KY; ²University of Cincinnati, Department of Dermatology, Cincinnati, OH; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Henry Ford Health System, West Bloomfield, MI; ⁵Celgene Corporation, Summit, NJ; ⁶Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ

Background/Objective: Patients with moderate plaque psoriasis (i.e., 5–10% psoriasis-involved Body Surface Area [BSA]) often receive no treatment or are undertreated with topical monotherapy. Plaque psoriasis that occurs in difficult-to-treat areas such as the scalp and nails might be disproportionately more distressing to patients because it is highly visible and can severely impact daily functioning. Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that works intracellularly to regulate inflammatory pathways relevant to the pathogenesis of psoriasis. Apremilast has been shown to be effective and has demonstrated acceptable tolerability in Phase IV clinical studies in patients with moderate-to-severe psoriasis. Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL; ClinicalTrials.gov: NCT02425826) is the first prospective, randomized, placebo (PBO)-controlled trial to demonstrate the clinical efficacy and safety of a systemic treatment (apremilast) in systemic- and biologic-naive patients with moderate plaque psoriasis. To further understand the efficacy of apremilast in patients with moderate plaque psoriasis, analyses were performed in the subset of patients with baseline scalp and/or nail involvement.

Methods: UNVEIL is a Phase IV, multicenter, randomized, PBO-controlled, double-blind study. Men and women at least 18 years of age with chronic plaque psoriasis for six months before screening were included in the study. Subjects had moderate plaque psoriasis at screening and baseline as defined by BSA of 5 to 10 percent and static Physician’s Global Assessment (sPGA) of 3 (moderate) based on a scale ranging from 0 (clear) to 5 (very severe). Included subjects had no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis. Potential subjects with an inflammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis, were excluded. Persons using topical therapy within two weeks or phototherapy within four weeks of randomization were also excluded. Patients were randomized (2:1) to receive apremilast 30mg twice daily (APR) or PBO during Weeks 0 to 16; patients in the PBO group were switched to APR at Week 16. All patients continued taking APR through Week 52. A nonmedicated moisturizer was the only topical therapy permitted during the study.

Patients with a baseline Scalp Physician Global Assessment (ScPGA) score of 1 or a Nail Psoriasis Severity Index (NAPSI) score of 1 in the target nail were included in subanalyses of scalp and nail involvement. ScPGA was assessed on a 6-point scale ranging from 0 (clear) to 5 (very severe). One thumbnail or fingernail with the worst nail psoriasis involvement at baseline was designated as the target nail. NAPSI score was calculated in the target nail as the sum of scores for the nail matrix and nail bed, with each score based on the number of quadrants with psoriasis features. Efficacy assessments in patients with scalp psoriasis at baseline included proportion of patients achieving ScPGA score of 0 (clear) or 1 (minimal), with a 2-point reduction from baseline score, at Week 16 and Week 52. Efficacy assessments in patients with nail psoriasis at baseline included change from baseline in NAPSI score at Week 16 and Week 52, proportion of patients achieving a 50-percent reduction from baseline in NAPSI score (NAPSI-50) at Week 16 and Week 52. Safety was evaluated based on adverse events (AEs), vital signs, clinical laboratory testing, and complete physical examinations. Efficacy and safety assessments were conducted for the intent-to-treat (ITT) population, which included all randomized patients; safety assessments included all patients who received one dose of study medication. The proportions of patients achieving ScPGA and NAPSI-50 responses were compared between the PBO and APR groups at Week 16 using a two-sided Cochran-Mantel-Haenszel test stratified by site. Changes from baseline in NAPSI score at Week 16 were compared between treatment groups using a two-way analysis of covariance (ANCOVA) model with treatment and site as factors and baseline value as a covariate. Efficacy parameters at Week 52 were evaluated descriptively. The last-observation-carried-forward (LOCF) methodology was used to impute missing values. Safety assessments were summarized using frequencies and percentages.

Results: A total of 221 patients were randomized to study treatment. Of these, 167 patients (75.6%) had scalp psoriasis and 83 patients (37.6%) had nail psoriasis at baseline. Demographic and baseline disease characteristics of the cohorts with scalp psoriasis or nail psoriasis were generally comparable between treatment groups. Mean baseline NAPSI scores were comparable between treatment groups. Across treatment groups, most patients had mild or moderate scalp involvement (i.e., ScPGA score of 2 or 3). Regarding efficacy of APR in scalp psoriasis, at Week 16, more patients treated with APR than with PBO achieved an ScPGA score of 0 or 1 with a 2-point reduction from baseline (38.4% vs. 20.0%, P=0.0178). At Week 52, patients remaining on APR maintained ScPGA response, and those who switched to APR from PBO at Week 16 (PBO/APR) demonstrated an improvement in ScPGA response comparable to those who continued APR treatment (APR/APR). An ScPGA score of 0 or 1 with a 2-point reduction from baseline was achieved by 47.7 percent of patients randomized to APR who continued on APR (APR/APR), and 46.9 percent of patients randomized to PBO who switched to APR (PBO/APR). Regarding the efficacy of APR in nail psoriasis, at Week 16, the mean percentage change from baseline in NAPSI score was -10.5 percent in the PBO group and -28.9 percent in the APR group (P=0.12). At Week 52, continued improvement in NAPSI score was seen in patients who remained on APR treatment (mean percentage change from baseline, -51.9%). Patients who switched from PBO to APR at Week 16 demonstrated an improvement in NAPSI score (mean percentage change from baseline, -52.7%). At Week 16, NAPSI-50 response was achieved by 18.5 percent of patients in the PBO group and 26.8 percent of patients in the APR group (P=0.50). Although differences in NAPSI-50 response with APR compared with PBO are numerically greater, the number of patients with nail psoriasis at baseline was low and thus statistical significance was not demonstrated. At Week 52, the proportion of patients who achieved NAPSI-50 response increased in patients who remained on APR treatment and in patients who switched to APR from PBO at Week 16.

The most common AEs reported with APR treatment from 0 to 52 weeks were diarrhea, nausea, headache, and nasopharyngitis. Most AEs were mild or moderate; discontinuations due to AEs occurred in 6.6 percent of patients over the 52-week study. The incidence of AEs, based on exposure-adjusted incidence rate (EAIR) per 100 patient-years, did not increase with longer exposure up to 52 weeks when compared with Weeks 0 to 16. No new safety or tolerability issues were observed up to 52 weeks.

Conclusion: APR treatment improved scalp and nail psoriasis at Week 16 in systemic- and biologic-naive patients with moderate plaque psoriasis (BSA 5–10%); continued improvement was seen with APR treatment up to 52 weeks. The efficacy of APR on scalp and nail psoriasis was consistent with that previously reported in patients with moderate-to-severe plaque psoriasis in randomized Phase III trials. The safety and tolerability profile of APR was also consistent with previous studies.

Funding/Disclosures: The authors acknowledge financial support for this study from Celgene Corporation. J. Mark Jackson provides research, honoraria, consulting, and/or other support to the Celgene Corporation. Ali Alikhan is a former speaker for Celgene Corporation. Mark Lebwohl is an investigator and/or consultant for the Celgene Corporation. Linda Stein Gold is an investigator and/or consultant for the Celgene Corporation. Joana Goncalves and Eugenia Levi are employees of the Celgene Corporation. Jerry Bagel is an advisory board member, speaker, consultant, and/or provides research support to the Celgene Corporation.