BACKGROUND: Data from early-stage studies suggested that @entity3646 and @entity4047 are requisite drivers of @entity483 , evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe @entity483 inadequately controlled by topical treatments. METHODS: In this randomised, placebo-controlled, double-blind study, we enrolled @entity1 aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (>= 16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. @entity1 were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. @entity1 on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned @entity1 who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988. FINDINGS: Between May 15, 2013, and Jan 27, 2014, 452 @entity1 were assessed for eligibility, and 380 @entity1 were randomly assigned. 379 @entity1 received one or more doses of study drug (300 mg once a week [n=63], 300 mg every 2 weeks [n=64], 200 mg every 2 weeks [n=61], 300 mg every 4 weeks [n=65], 100 mg every 4 weeks [n=65]; placebo [n=61]). EASI score improvements favoured all dupilumab regimens versus placebo (p<0  0001): 300 mg once a week (-74% [SE 5  16]), 300 mg every 2 weeks (-68% [5  12]), 200 mg every 2 weeks (-65% [5  19]), 300 mg every 4 weeks (-64% [4  94]), 100 mg every 4 weeks (-45% [4  99]); placebo (-18% [5  20]). 258 (81%) of 318 @entity1 given dupilumab and 49 (80%) of 61 @entity1 given placebo reported treatment-emergent adverse events; @entity11266 was the most frequent (28% and 26%, respectively). INTERPRETATION: Dupilumab improved clinical responses in adults with moderate-to-severe @entity483 in a dose-dependent manner, without significant safety concerns. Our findings show that @entity3646 and @entity4047 are key drivers of @entity483 . FUNDING: Sanofi and Regeneron Pharmaceuticals.

Efficacy and safety of dupilumab in adults with moderate-to-severe XXXX inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity483 :: ('MESH:D003876', 'Disease') :: ['atopic dermatitis'] @entity11266 :: ('MESH:D009304', 'Disease') :: ['nasopharyngitis'] @entity4047 :: ('3596', 'Gene') :: ['IL-13'] @entity3646 :: ('3565', 'Gene') :: ['IL-4', 'interleukin (IL)-4']
@entity483 :: (MESH:D003876,Disease) :: ['atopic dermatitis']
