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

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.

Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases

“…The 35 included trials were published between 2015 and 2023 with an almost equal proportion of female and male participants (male, 54%); mean (SD) age was 38.5 (10.1) years. The baseline characteristics of the study populations are provided in the Table …”

Model of Chronic Itch in Aged Mice: Beneficial Effects of Drugs Affecting Descending Modulatory Systems

“…3b ). Baricitinib and abrocitinib are approved in many countries for the treatment of moderate-to-severe AD in adults ( 28 , 29 ), but not for dermal pruritus without skin lesions, at least in Japan ( 7 ). It is believed that JAK inhibitors are effective for AD primarily by suppressing Th2 inflammation via inhibiting JAK-STAT signalling ( 30 ).…”

Comparison of Old and New Systemic Treatments for Moderate to Severe Atopic Dermatitis

“…A phase 3, (RDBPC) study (BREEZE-AD PEDS) randomized participants aged 2 to < 18 years old (1:1:1:1) to baricitinib 1mg, 2mg, 4mg, and placebo daily for 16 weeks [ 50 ]. The results are as follows, respectively, for baricitinib 1mg, 2mg, 4mg, and placebo: vIGA-AD 18.2%, 25.8%, 41.7%, 16.4% (primary endpoint), with 4mg baricitinib being superior to placebo; EASI-75 32.2%, 40%, 52.5%, 32%; EASI-90 11.6%, 21.7%, 30%, placebo 12.3%; SCSORAD 75 7.4%, 15.8%, 20%, 9.8%; EASI change from baseline 15.67, 15.83, 16.88, 14.16; NRS ≥ 4 for itch 17.5%, 26.8%, 35.5%, 16.4%.…”