52-week ivarmacitinib in moderate-to-severe atopic dermatitis: A phase 3 trial.

BACKGROUND: Ivarmacitinib, an oral JAK1 inhibitor, improved efficacy outcomes versus placebo at Week 16 in a phase 3 trial in patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To describe efficacy and safety outcomes through Week 52. METHODS: In this multicentre, double-blind, phase 3 trial (NCT04875169), patients aged 12-75 years were randomized 1:1:1 to receive once-daily oral ivarmacitinib 4 mg, ivarmacitinib 8 mg, or placebo for 16 weeks, followed by a 36-week double-blind extension. At Week 16, placebo-treated patients who continued in the study were re-randomized to ivarmacitinib 4 mg or 8 mg. Key Week 52 endpoints included Investigator's Global Assessment (IGA) 0/1 with at least a 2-grade improvement, Eczema Area and Severity Index 75 (EASI-75), and Worst Itch Numeric Rating Scale (WI-NRS) response. RESULTS: Of 336 randomized patients, 258 completed 52 weeks of treatment. Among patients initially randomized to ivarmacitinib, Week 52 IGA responses were achieved by 42.3% and 40.2% of patients in the 4 mg and 8 mg groups, respectively. EASI-75 responses were achieved by 60.6% and 55.9%, and WI-NRS responses by 59.6% and 45.1%, respectively. During the active-treatment period, treatment-emergent adverse events (TEAEs) occurred in 87.5% and 85.5% of patients in the 4 mg and 8 mg groups, respectively. The most frequent TEAEs were upper respiratory tract infection, COVID-19, SARS-CoV-2 test positive, and increased blood creatine phosphokinase. Serious TEAEs occurred in 5.6% and 4.4% of patients, respectively. CONCLUSION: Ivarmacitinib was associated with generally maintained improvement through Week 52, with a safety profile generally consistent with that observed during the placebo-controlled period. Because the extension phase had no placebo control after Week 16, long-term efficacy findings should be interpreted as descriptive.