Dupilumab Monotherapy in Adults with Moderate-to-Severe Atopic Dermatitis: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study

RATIONALE: Dupilumab, a human monoclonal antibody targeting the IL-4Rα subunit, blocks IL-4/IL-13 signaling.

METHODS: This European trial randomized adults with moderate-to-severe atopic dermatitis poorly controlled by topical agents to 12 weekly subcutaneous doses of placebo (n=54) or dupilumab 300 mg (n=55); topical agents were not permitted. Primary efficacy endpoint was percent change in Eczema Area and Severity Index (EASI) score from baseline to week 12. Secondary endpoints included changes from baseline in EASI, body surface area, SCORAD, pruritus numerical rating scale, and 5-D Pruritus Scale; proportions of patients achieving EASI reduction ≥50% (EASI-50), Investigator's Global Assessment (IGA) 0 or 1, and safety were assessed.

RESULTS: Baseline characteristics were similar between groups (EASI mean ±SD: 23.12±12.35 on dupilumab and 24.10±12.70 on placebo). Percent change from baseline in EASI showed improvements that significantly favored dupilumab relative to placebo, -74.0% and -23.3%, respectively (P<0.0001). EASI-50 responder rate was 85.5% with dupilumab and 35.2% with placebo (P<0.0001).  Other measures of disease activity (SCORAD and IGA) and pruritus scores significantly favored dupilumab (P<0.0001). Eleven SAEs were reported in the placebo group compared to 1 in the dupilumab group. Skin infections were also reported less often in dupilumab group (2[4%] vs 14[26%]). Treatment-emergent adverse events (TEAEs) were 74.5% with dupilumab and 77.8% with placebo. Frequent TEAEs reported more often with dupilumab were injection site reactions and nasopharyngitis.

CONCLUSIONS:  In this study, 12 weeks of dupilumab monotherapy was associated with rapid, marked improvements in measures of disease activity and pruritus, fewer SAEs, less infections compared to placebo, and was generally well-tolerated.