Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from two phase III trials

Background In the U.S.A., an Investigator's Global Assessment (IGA) score of <= 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods LIBERTY AD SOLO 1 and 2 were two 16-week, randomized, double-blind trials enrolling adult patients with moderate-to-severe AD (IGA >= 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results At week 16, 278 of 449 dupilumab q2w-treated patients (median age 36 center dot 0 years) and 396 of 443 placebo-treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (-48 center dot 9% vs. -11 center dot 3%, P < 0 center dot 001), pruritus NRS (-35 center dot 2% vs. -9 center dot 1%, P < 0 center dot 001), affected BSA (-23 center dot 1% vs. -4 center dot 5%, P < 0 center dot 001), POEM score >= 4-point improvement (57 center dot 4% vs. 21 center dot 0%, P < 0 center dot 001) and DLQI score >= 4-point improvement (59 center dot 3% vs. 24 center dot 4%, P < 0 center dot 001). Conclusions In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA <= 1 end point significantly underestimates clinically relevant dupilumab treatment effects.