Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, shows efficacy in patients with active nonsegmental vitiligo and either a lighter or darker Fitzpatrick skin type: results from a phase 2b, randomized, dose-ranging study with an extension period

Abstract

Abstract Ritlecitinib, an oral JAK3/TEC inhibitor, inhibits cytokines IL-15 and IFN-γ that play a critical role in vitiligo pathogenesis. In a phase 2b trial, ritlecitinib demonstrated a significant improvement on the centrally read Facial Vitiligo Area Scoring Index (crF-VASI) at Week 24 in patients with active nonsegmental vitiligo (NSV) at 50 mg daily with or without a loading dose (100 or 200 mg daily for 4 weeks). Improvement on the crF-VASI was observed up to Week 48 in patients receiving ritlecitinib 50 mg daily with a 200 mg daily loading dose for 4 weeks in the 24-week extension period. We evaluated the efficacy and safety of ritlecitinib, an oral JAK3/TEC inhibitor, in patients with active NSV and lighter Fitzpatrick skin types (FST; I–III) or darker FST (IV–VI) from the Phase 2b study (NCT03715829). Patients with active NSV were randomized to placebo or ritlecitinib 50 mg daily with or without a loading dose (200 or 100 mg, 4-week) or low doses (30 or 10 mg) in a 24-week, dose-ranging period, followed by a 24-week extension wherein patients were allocated to 200/50 mg (200 mg, 4-week; 50 mg, 20-week). Percent change from baseline (%CFB) in F-VASI was evaluated. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs). A total of 253 patients (lighter FST, n = 170; darker FST, n = 83) completed the dose-ranging period. Placebo-adjusted mean %CFB in F-VASI at Week 24 among the 50 mg and low-dose groups, respectively, were −15·2 (P = 0·0043) and −5·5 (P = 0·1991) in lighter FST and −37·4 (P < 0·0001) and −15·7 (P = 0·0401) in darker FST. In the extension, 187 patients received 200/50 mg and 136 (lighter FST, n = 96; darker FST, n = 40) completed Week 48. Continuous re-pigmentation without plateau of effect was observed across FST through Week 48; mean %CFB in F-VASI at Week 48 in patients initially treated with 50 mg, low doses or placebo in the dose-ranging period, respectively, were −63·1, −51·0 and −51·3 for lighter FST and −66·8, −51·0 and −52·5 for darker FST. TEAE incidence in the dose-ranging period was similar between lighter and darker FST (range, 69·2–81·0%). Ritlecitinib was generally safe with similar efficacy in vitiligo patients with lighter or darker FST.