Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical t

Abstract

SummaryBackground Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective in all patients with atopic dermatitis, and sideeffects limit its use. Dupilumab, a fully human anti-interleukin 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 European Union for the treatment of inadequately-controlled moderate-to-severe atopic dermatitis in adults. Objectives To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic dermatitis with inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. Methods In this 16-week, double-blind, randomized, placebo-controlled, phase III trial, patients were randomized 1 : 1 : 1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo. All received concomitant medium-potency TCS from Week À2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS. Results In total, 390 patients were screened, 325 were randomized, and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the placebo + TCS group (primary end point) (59Á1% and 62Á6% vs. 29Á6%, respectively; P < 0Á001 vs. placebo + TCS, both doses). Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS

Fifty‐two week follow‐up safety and effectiveness results of dupilumab treatment of moderate‐to‐severe atopic dermatitis from a retrospective, multicentric series

“…The clinical safety and effectiveness of dupilumab in our series were consistent with those observed in clinical trials (Beck et al, 2014;Blauvelt et al, 2017;de Bruin-Weller et al, 2018;Simpson, Gadkari, et al, 2016;Thaçi et al, 2016).…”

Real‐world use of dupilumab for 53 patients with atopic dermatitis in Japan

“…Dupilumab-induced conjunctivitis was more frequent in patients with a previous history of conjunctivitis (6/15 patients, 40%) than in those with no history of conjunctivitis (4/38 patients, 10.5%), which is comparable to clinical trial findings. 5,6 Despite the short follow-up period and small sample, this study indicates that dupilumab is effective in treating patients with moderate-to-severe AD in daily practice. TARC reduction, however, did not necessarily reflect improved AD.…”

Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre

“…Although these results also include some patients transferred from other systemic treatments with initial EASI score values below 16, the results are in accordance with the previously reported results on efficacy of dupilumab in phase 3 clinical trials (SOLO 1, SOLO 2, CHRONOS and CAF E). [13][14][15] In the present study, the effectiveness of dupilumab evaluated by percentage reduction in EASI score, EASI-50 and EASI-75 at week 12 was similar to results obtained from clinical trials of dupilumab in combination with topical corticosteroids (CAF E, EASI-75: 62% and CHRONOS, EASI-75: 69%) 14,15 and was slightly higher than the efficacy in trials with dupilumab as monotherapy (SOLO 1, EASI-75: 51.3% and SOLO 2, EASI-75: 44.2%). 13 This was expected, as concomitant treatment with topical anti-inflammatory agents is common practice in the clinical setting and to a major degree self-administered in this group of chronic patients.…”