Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial

Abstract

Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies.

Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy.

Design, setting, and participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study.

Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed.

Main outcomes and measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16.

Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis.

Conclusions and relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD.

Trial registration: ClinicalTrials.gov Identifier: NCT03733301.

Figure 1.. CONSORT Diagram

TCS indicates topical corticosteroid. ^aOne patient failed screening and was randomized in error, and 1 patient was noncompliant with study visits.

Figure 2.. Efficacy and Health Outcomes

Data were assessed for patients in the intention-to-treat population and analyzed with a logistic regression model with nonresponder imputation for response rates and mixed-models repeated-measure analysis or analysis of covariance for least-squares mean change from baseline. ADSS indicates Atopic Dermatitis Sleep Scale; EASI, Eczema Area and Severity Index; NRS, Numeric Rating Scale; TCS, topical corticosteroid; and vIGA-AD, validated Investigator Global Assessment for Atopic Dermatitis. ^aAssessed for patients with a baseline Itch NRS score of 4 or greater. ^bAssessed for patients with a baseline Skin Pain NRS score of 4 or greater. ^cAssessed for patients with a baseline ADSS Item 2 score greater than 1.