Dupilumab in Adults With Moderate to Severe Atopic Dermatitis A 5-Year Open-Label Extension Study

Beck LA, Bissonnette R, Deleuran M, et al. JAMA Dermatol. Published online July 10, 2024. doi:10.1001/jamadermatol.2024.1536

Key Points

Question  What is the long-term safety and efficacy of dupilumab in adults with moderate to severe atopic dermatitis?

Findings  In this open-label extension study of 2677 adults with moderate to severe atopic dermatitis, dupilumab was well tolerated with no new safety incidents and showed sustained efficacy (including improvements in atopic dermatitis signs, symptoms, and quality of life) for up to 5 years.

Meaning  These data support the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe atopic dermatitis, confirming previous data demonstrating sustained efficacy with an acceptable safety profile.

Abstract

Importance  Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important.

Objective  To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD.

Design, Setting, and Participants  The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023.

Exposures  At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals.

Main Outcomes and Measures  The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline.

Improvement in Eczema Area and Severity Index (EASI) Score Over Time

Results  A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study.

Conclusions and Relevance  In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

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