Ivarmacitinib for the treatment of adults with severe alopecia areata: Results from a phase 3 trial.

Abstract

Ivarmacitinib, a selective Janus kinase 1 (JAK1) inhibitor, demonstrated efficacy in a phase 2 trial for moderate-to-severe alopecia areata (AA). To evaluate the efficacy and safety of ivarmacitinib in adults with severe AA (≥50% scalp hair loss, including alopecia totalis/universalis). In this randomized, double-blind, phase 3 trial, 330 patients were assigned (1:1:1) to ivarmacitinib 4 mg, 8 mg, or placebo once daily for 24 weeks. Placebo recipients were re-randomized to ivarmacitinib for a 28-week extension. The primary endpoint was the proportion achieving a Severity of Alopecia Tool (SALT) score ≤20 at week 24. At week 24, SALT ≤20 was achieved by 34.9% (4 mg), 40.6% (8 mg), and 9.0% (placebo). Absolute differences versus placebo were 25.6% (95% CI: 15.4-35.7) for 4 mg and 31.6% (21.5-41.8) for 8 mg (both P < .0001). Treatment-emergent adverse events occurred in 77.1%, 84.7%, and 75.5% of patients, respectively; most were mild or moderate. No deaths, major cardiovascular events, or thromboembolic events were reported. No active comparator was used. Once-daily ivarmacitinib 4 mg or 8 mg resulted in meaningful hair regrowth and demonstrated an acceptable safety profile in patients with severe AA.