Long-Term Management Of Moderate-To-Severe Atopic Dermatitis With Dupilumab And Concomitant Topical Corticosteroids: A 1-Year Randomized, Placebo-Controlled Phase 3 Trial (Chronos)

The long-term efficacy and safety of dupilumab, a fully human anti-interleukin-4-receptor-alpha monoclonal antibody, plus concomitant topical corticosteroids (TCS) were evaluated in patients with moderate-to-severe atopic dermatitis (AD). CHRONOS (ClinicalTrials.gov: NCT02260986) was a 1-year, double-blind, randomised, placebo-controlled, parallel-group, phase 3 study in adults with moderate-to-severe AD and an inadequate response to TCS. Patients were randomised 3:1:3 to dupilumab 300 mg every week (qw), 300 mg every 2 weeks (q2w), or placebo. Patients received a standardised regimen of concomitant low-/medium-potency TCS that could be tapered or stopped as necessary or topical calcineurin inhibitors in areas inadvisable for TCS. Efficacy data were available for 740 (Week 16) and 623 (Week 52) patients; safety data for 740 patients (Week 52). Significantly more patients receiving dupilumab + TCS achieved an Investigator’s Global Assessment score 0/1 and ≥ 2-point improvement from baseline (Week 16: 39.2%/38.7% vs 12.4% [qw + TCS/q2w + TCS vs placebo + TCS]; Week 52: 40.0%/36.0% vs 12.5%), 50% improvement in Eczema Area and Severity Index (EASI-50) (Week 16: 78.1%/80.2% vs 37.5%; Week 52: 70.0%/78.7% vs 29.9%), EASI-75 (Week 16: 63.9%/68.9% vs 23.2%; Week 52: 64.1%/65.2% vs 21.6%), EASI-90 (Week 16: 43.3%/39.6% vs 11.1%; Week 52: 50.7%/50.6% vs 15.5%), or a ≥ 4-point improvement in peak pruritus Numerical Rating Scale (Week 16: 50.8%/58.8% vs 19.7%; Week 52: 39.0%/51.2% vs 12.9%) (P < 0.0001 vs placebo + TCS, each comparison). Treatment groups had similar adverse/serious adverse event rates and no significant laboratory abnormalities. Dupilumab + TCS-treated patients reported numerically higher rates of conjunctivitis (19.4%/13.6% vs 7.9%) and injection-site reactions (20.0%/16.4% vs 7.9%); placebo + TCS-treated patients reported more non-herpetic skin infections (8.3%/10.9% vs 17.8%) and AD flares (12.7%/13.6% vs 41.3%). Long-term treatment with dupilumab and concomitant topical medications significantly improved AD signs and symptoms, including pruritus, and showed an acceptable safety profile. Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifier: NCT02260986. Editorial assistance provided by Manuela Pigors, PhD and Sven Holm, PhD of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Refer to poster.