Dupilumab with concomitant topical corticosteroids in adult patients with atopic dermatitis who are not adequately controlled with or are intolerant to ciclosporin A, or when this treatment is medically inadvisable: a placebo-controlled, randomized phase 3 clinical trial (LIBERTY AD CAFÉ)

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely-used, potent immunosuppressant for AD. CsA is not effective in all patients, and side effects limit its use. Dupilumab, a fully human anti-interleukin (IL)-4 receptor-alpha monoclonal antibody, inhibits signaling of IL-4 and IL-13, key drivers of type 2/Th2-mediated inflammation, and is approved in the U.S.A. and the E.U. for the treatment of adults with moderate-to-severe AD. OBJECTIVES: To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with AD with inadequate response to/intolerance of CsA, or for whom CsA was medically inadvisable. METHODS: In this 16-week, double-blind, randomized, placebo-controlled, phase 3 trial, patients were randomized 1:1:1 to subcutaneous dupilumab 300 mg weekly (qw):every two weeks (q2w):placebo. All received concomitant medium-potency TCS from Week -2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS. RESULTS: 390 patients were screened; 325 were randomized and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients on dupilumab qw+TCS/q2w+TCS achieved ≥75% improvement from baseline in Eczema Area and Severity Index at Week 16 vs placebo+TCS (primary endpoint) (59.1%/62.6% vs 29.6%; P<0.0001 vs placebo+TCS, both doses). Dupilumab qw+TCS/q2w+TCS significantly improved other clinical outcomes and AD symptoms, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QOL). Treatment groups had similar overall rates of adverse events (69.1%/72.0%/69.4%; qw+TCS/q2w+TCS/placebo+TCS) and serious adverse events (1.8%/1.9%/1.9%). Conjunctivitis was more frequent with dupilumab+TCS; skin infections were more frequent with placebo+TCS. CONCLUSIONS: Dupilumab+TCS significantly improved signs and symptoms of AD and QOL in adults with history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified. This article is protected by copyright. All rights reserved.