Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

Abstract

Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200mg and 100mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200mg) than dupilumab at week2. This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a posthoc analysis of the JADE COMPARE trial. Adults with moderate-to-severe AD received once-daily oral abrocitinib 200mg or 100mg, dupilumab 300mg subcutaneous injection every 2weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator's Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥2-point improvement from baseline, ≥75% and ≥90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days2-15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week16. The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200mg than placebo (nominal p <0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200mg than placebo (nominal p <0.01); the time to achieve this response was shorter with abrocitinib 200mg (range 4.5-6.0days) than abrocitinib 100mg (range 5.0-17.0days), dupilumab (range 8.0-11.0 days), and placebo (range 3.0-11.5days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200mg than placebo (nominal p <0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy. Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD. ClinicalTrials.gov, NCT03720470.