Dupilumab with concomitant topical corticosteroids in moderate-to-severe atopic dermatitis: A randomised, placebo-controlled phase 3 clinical trial (CHRONOS)

Background: In previous 16-week monotherapy studies, dupilumab, an anti-interleukin-4 receptor-α monoclonal antibody, significantly improved signs and symptoms with acceptable safety in patients with moderate-to-severe atopic dermatitis (AD).
Methods: This randomised, placebo-controlled, double-blind, phase 3 study (NCT02260986) evaluated 1-year safety and efficacy of dupilumab with concomitant topical corticosteroids (TCS). Adults with moderate-to-severe AD and inadequate response to TCS were randomized 3:1:3 to dupilumab 300mg weekly (qw), 300mg every 2 weeks (q2w), and placebo; all received concomitant TCS.
Results: Data were available for all 740 randomised patients at Week 16 and 623 at Week 52. At Week 16, significantly more dupilumab+TCS-treated patients vs placebo+TCS achieved Investigator’s Global Assessment (IGA) 0/1 (clear/almost clear) (qw+TCS/q2w+TCS vs placebo+TCS: 39.2%/38.7% vs 12.4%; P<0.0001, for each dose group [primary endpoint]), Eczema Area and Severity Index-75% improvement (EASI-75) (63.9%/68.9% vs 23.2%; P<0.0001 for each), and pruritus numerical rating scale (NRS) ≥4-point improvement (50.8%/58.8% vs 19.7%; P<0.0001 for each). Similarly, at Week 52, significantly more dupilumab+TCS-treated patients achieved IGA 0/1 (40.0%/36.0% vs 12.5%; P<0.0001 for each), EASI-75 (64.1%/65.2% vs 21.6%; P<0.0001 for each), and pruritus NRS improvement ≥4 (39.0%/51.2% vs 12.9%; P<0.0001 for each). In the safety analysis set during treatment period (N=740), dupilumab+TCS-treated patients reported higher rates of conjunctivitis (19.4%/13.6% vs 7.9%) and injection-site reactions (20.0%/16.4% vs 7.9%); conversely, non-herpetic skin infections (8.3%/10.9% vs 17.8%) and dermatitis atopic events (16.5%/18.2% vs 45.7%) were more frequent in placebo+TCS-treated patients.
Conclusions: One year of treatment with dupilumab+TCS in moderate-to-severe AD significantly improves signs and symptoms vs placebo+TCS, with acceptable safety.

A/Prof Peter Foley