Efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate-to-severe atopic dermatitis with inadequate response to topical corticosteroids: results from a phase 3, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS)

Torrelo A, Rewerska B, Galimberti M, Paller A, Yang CY, Prakash A, Zhu D, Pontes Filho MAG, Wu WS, Eichenfield L. Efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate-to-severe atopic dermatitis with inadequate response to topical corticosteroids: results from a phase 3, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS). Br J Dermatol. 2023 Mar 31:ljad096. doi: 10.1093/bjd/ljad096.

Abstract

Background

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved in many countries for moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic therapy.

Objectives

To evaluate the efficacy and safety of three doses of baricitinib in combination with low-to-moderate potency topical corticosteroids in pediatric patients with moderate-to-severe AD.

Methods

Patients (aged 2 to <18 years) were randomized (1:1:1:1) to once-daily baricitinib low dose (1-mg equivalent), medium dose (2-mg equivalent), high dose (4-mg equivalent), or placebo for 16 weeks. The primary endpoint was the proportion of patients achieving a validated Investigator Global Assessment® (vIGA-AD) of 0/1 with a ≥ 2-point improvement at week 16. Key secondary endpoints included proportions of patients achieving 75% and 90% improvement in the Eczema Area and Severity Index (EASI75, EASI90), 75% improvement in the SCORing Atopic Dermatitis (SCORAD75), mean change from baseline in EASI score, and proportion of patients achieving a 4-point improvement in the Itch Numeric Rating scale (NRS) for patients ≥10 years. Primary and key secondary efficacy analyses were conducted on the intent-to-treat population and adjusted for multiplicity. Safety analyses included all randomized patients who received ≥1 dose of study treatment.

Results

A total of 483 patients were randomized (mean age: 12 years). Baricitinib 4-mg equivalent achieved statistically significant (P < 0.05) improvement versus placebo on all 16-week endpoints (vIGA 0/1 with ≥2-point improvement, EASI75, EASI90, SCORAD75, mean change EASI score, and Itch NRS 4-point improvement for patients ≥10 years). Improvement (P < 0.05 non-multiplicity adjusted) was also observed for baricitinib 4-mg equivalent versus placebo in the ability to fall asleep and in reduction of topical corticosteroid use. Few patients discontinued due to adverse events (1.6% for placebo and 0.6% for baricitinib-treated). There were no deaths, venous thromboembolic events, arterial thrombotic events, major adverse cardiovascular events, malignancies, gastrointestinal perforations, or opportunistic infections.

Discussion

Study results indicate that baricitinib offers a potential therapeutic option with a favorable benefit-risk profile for pediatric patients with moderate-to-severe AD who are candidates for systemic therapies.

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