BACKGROUND: Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) 
blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines 
implicated in numerous allergic diseases ranging from asthma to atopic 
dermatitis. Previous 16-week monotherapy studies showed that dupilumab 
substantially improved signs and symptoms of moderate-to-severe atopic 
dermatitis with acceptable safety, validating the crucial role of interleukin 4 
and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the 
long-term efficacy and safety of dupilumab with medium-potency topical 
corticosteroids versus placebo with topical corticosteroids in adults with 
moderate-to-severe atopic dermatitis.
METHODS: In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 
study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and 
inadequate response to topical corticosteroids were enrolled at 161 hospitals, 
clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and 
North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 
300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a 
central interactive voice/web response system, stratified by severity and global 
region. All three groups were given concomitant topical corticosteroids with or 
without topical calcineurin inhibitors where inadvisable for topical 
corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted 
on the basis of disease activity. Coprimary endpoints were patients (%) 
achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher 
improvement from baseline, and Eczema Area and Severity Index 75% improvement 
from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses 
included all randomised patients; week 52 efficacy included patients who 
completed treatment by US regulatory submission cutoff. This study is registered 
with ClinicalTrials.gov, NCT02260986.
FINDINGS: Between Oct 3, 2014, and July 31, 2015, 740 patients were enrolled: 
319 were randomly assigned to dupilumab qw plus topical corticosteroids, 106 to 
dupilumab q2w plus topical corticosteroids, and 315 to placebo plus topical 
corticosteroids. 623 (270, 89, and 264, respectively) were evaluable for week 52 
efficacy. At week 16, more patients who received dupilumab plus topical 
corticosteroids achieved the coprimary endpoints of IGA 0/1 (39% [125 patients] 
who received dupilumab plus topical corticosteroids qw and 39% [41 patients] who 
received dupilumab q2w plus topical corticosteroids vs 12% [39 patients] who 
received placebo plus topical corticosteroids; p<0·0001) and EASI-75 (64% [204] 
and 69% [73] vs 23% [73]; p<0·0001). Week 52 results were similar. Adverse 
events were reported in 261 (83%) patients who received dupilumab qw plus 
topical corticosteroids, 97 (88%) patients who received dupilumab q2w, and 266 
(84%) patients who received placebo, and serious adverse events in nine (3%), 
four (4%), and 16 (5%) patients, respectively. No significant dupilumab-induced 
laboratory abnormalities were noted. Injection-site reactions and conjunctivitis 
were more common in patients treated with dupilumab plus topical 
corticosteroids-treated patients than in patients treated with placebo plus 
topical corticosteroids.
INTERPRETATION: Dupilumab added to standard topical corticosteroid treatment for 
1 year improved atopic dermatitis signs and symptoms, with acceptable safety.
FUNDING: Sanofi and Regeneron Pharmaceuticals Inc.