Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib in patients with extensive vitiligo in a phase 2, randomized, double-blinded, dose-ranging, placebo-controlled study

BACKGROUND: No repigmentation treatments are approved for vitiligo affecting > 10% body surface area. OBJECTIVE: To assess efficacy and safety of povorcitinib (oral, selective Janus kinase 1 inhibitor) in extensive nonsegmental vitiligo. METHODS: This double-blinded, placebo-controlled, dose-ranging phase 2 study (NCT04818346) randomized adult patients 1:1:1:1 to once-daily povorcitinib 15, 45, or 75 mg or placebo for 24 weeks. Subsequently, patients received povorcitinib 45 mg (initially randomized to 45 mg) or 75 mg (initially randomized to placebo, 15, or 75 mg) until week 52, followed by 24-week post-treatment follow-up. Primary endpoint was percentage change from baseline in total Vitiligo Area Scoring Index (T-VASI) at week 24. RESULTS: Of 171 patients (mean total body surface area/T-VASI, 28.2%/25.5) randomized, 82.5% completed the 24-week treatment. At week 24, povorcitinib significantly improved T-VASI from baseline (15 mg, 19.1%; 45 mg, 17.8%; 75 mg, 15.7%) versus placebo (-2.3%; least squares mean povorcitinib vs placebo, P < .01). Continuous improvement was observed through week 52. Incidence of grade ≥ 3 treatment-emergent adverse events was similar across treatment groups, with no new safety signals. LIMITATIONS: Limited demographic diversity. CONCLUSION: Povorcitinib demonstrated substantial total body and facial repigmentation in adult patients with extensive nonsegmental vitiligo and was generally well tolerated through 52 weeks of treatment.