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.