The Safety Data of Dupilumab for the Treatment of Moderate‑to‑Severe Atopic Dermatitis in Infants, Children, Adolescents, and Adults.

Abstract

Background: Atopic dermatitis (AD) significantly affects quality of life in patients of all ages and requires long-term treatment. Dupilumab is approved for uncontrolled moderate-to-severe AD in patients aged ≥ 6 months and in other type 2 inflammatory diseases. Data from placebo-controlled, randomized clinical trials (RCTs) and long-term open-label extensions (OLEs) enable comprehensive assessment of dupilumab's safety profile for up to 5 years.

Objective: To integrate short- and long-term dupilumab safety data in patients with moderate-to-severe AD.

Methods: We describe safety from eight phase 3 trials with > 7000 patient-years of dupilumab use: five 16-week RCTs in children (6 months-11 years, with concomitant topical corticosteroids [TCS]) and adolescents and adults (≥ 12 years, without TCS); one 52-week RCT in adults (with TCS); and two OLEs in children and adolescents (6-11- and 12-18-year cohorts, ± TCS, duration ≤ 1 year) and adults (± TCS, duration ≤ 5 years).

Results: The proportion of patients experiencing ≥ 1 treatment-emergent adverse event (TEAE) in RCTs was lower with dupilumab versus placebo in children/infants and was similar with dupilumab versus placebo in adults/adolescents. Exposure-adjusted incidence rates with longer-term treatment in OLEs were similar to the RCTs. Most TEAEs reported in RCT and OLE studies were mild to moderate and not related to study drug (per investigators). Fewer patients in the dupilumab versus placebo treatment arms experienced serious TEAEs (16-week RCTs: infants/children 0.8% vs 3.0%; adults/adolescents 2.0-2.2% vs 4.6%; 52-week RCT: 3.2-3.6% vs 5.1%). Common TEAEs that had higher incidence rates with dupilumab compared with placebo in RCTs included injection-site reactions (Medical Dictionary for Regulatory Activities High Level Term) and conjunctivitis (clustered term). Serious infections and non-herpetic skin infections were more frequent with placebo.

Conclusions: In the most comprehensive dupilumab safety assessment to date, safety was consistent with the known dupilumab safety profile. [Graphical abstract and video abstract available.] TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03346434; NCT03345914; NCT03054428; NCT02277743; NCT02277769; NCT02260986; NCT01949311; NCT02612454. EudraCT: 2016-000955-28; 2016-004997-16; 2015-004458-16; 2014-001198-15; 2014-002619-40; 2013-003254-24; 2013-001449-15; 2015-001396-40. The Safety Data of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Infants, Children,Adolescents, and Adults(MP4 64,891 KB).