426 Efficacy and safety of abrocitinib in adolescents with moderate-to-severe atopic dermatitis from the JADE clinical trial program

Abstract Once-daily oral abrocitinib, a Janus kinase 1-selective inhibitor, was effective and well tolerated as a monotherapy in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD), as well as in combination with medicated topical therapy in adolescents with moderate-to-severe AD. This study aims to investigate efficacy and safety of abrocitinib in adolescents with moderate-to-severe AD from the JADE clinical trial program. Patients aged 12–17 years with moderate-to-severe AD and an inadequate response to ≥4 consecutive weeks of topical medication or treatment with systemic therapy for AD, both within the past 6 months, were randomly assigned [2:2:1 JADE MONO-1/MONO-2 (NCT03349060/NCT03575871); 1:1:1 JADE TEEN (NCT03796676)] to receive once-daily oral abrocitinib (200 or 100 mg) or placebo as monotherapy (JADE MONO-1 and JADE MONO-2) or in combination with medicated topical therapy (JADE TEEN) for 12 weeks. Coprimary endpoints were proportion of patients achieving Investigator’s Global Assessment (IGA) response [clear (0) or almost clear (1) with ≥2-grade improvement from baseline] and proportion of patients who achieved ≥75% improvement in Eczema Area and Severity Index score (EASI-75) at Week 12. A key secondary endpoint was the proportion of patients achieving ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4; used with permission from Regeneron Pharmaceuticals and Sanofi) at Week 12. Drug safety was also assessed. Overall, 285 and 124 adolescents in JADE TEEN and JADE MONO-1/MONO-2, respectively, were treated. In JADE TEEN, more abrocitinib-treated (200 mg, 100 mg) than placebo-treated patients achieved IGA (46.2%, 41.6% vs. 24.5%; P < 0.05 for both doses), EASI-75 (72.0%, 68.5% vs. 41.5%; P < 0.05 for both doses) and PP-NRS4 (55.4%, 52.6% vs. 29.8%; P < 0.01 for 200 mg vs. placebo) responses at Week 12. Adverse events (AEs) were reported for 62.8%, 56.8% and 52.1% of patients in 200 mg, 100 mg and placebo groups, respectively; 1 (1.1%), 0 and 2 patients (2.1%) had serious AEs. JADE MONO-1/MONO-2 safety results were similar, but efficacy results were lower, as expected for monotherapies. Results from JADE clinical trials suggest that abrocitinib was effective in adolescents with moderate-to-severe AD, with an acceptable safety profile.