Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, stabilizes active lesions and promotes re-pigmentation of stable lesions in patients with active nonsegmental vitiligo: results from a phase 2b, randomized, placebo-controlled, dose-ranging study

Abstract

Abstract Patients with active nonsegmental vitiligo (NSV) may experience active lesions (confetti-like and trichrome lesions) or stable lesions (where lesions may remain unchanged for ∼1 year or more). In a phase 2b trial, the oral JAK3/TEC inhibitor ritlecitinib demonstrated a significant improvement in the Facial-Vitiligo Area Scoring Index at Week 24 for patients with active NSV at 50 mg daily with or without a loading dose (100 or 200 mg daily for 4 weeks). To evaluate the efficacy of ritlecitinib on active vs. stable lesions in patients with active NSV who participated in the phase 2b trial (NCT0371529). Patients were randomized to daily ritlecitinib or placebo for 24 weeks, with or without a 4-week loading dose: 200/50, 100/50, 50, 30, 10 mg, or placebo. Mean percent change from baseline (%CFB) in depigmentation extent (100%, 90%, 75%, 50%, 25%, or 10%) within the lesion at baseline and Week 24 was evaluated centrally using photographs obtained from both active (clinical signs including confetti-like and trichrome lesions) and stable target lesions, other than on the face. The analysis included 317 patients who had active and stable lesions simultaneously among 364 treated patients. Within active lesions, ritlecitinib induced a statistically significant reduction in depigmentation extent [%CFB: 200/50 mg, +0·8 (P = 0·0388); 100/50 mg, −1·7 (P = 0·0035); 30 mg, −1·6 (P = 0·0086)] compared with a progressive increase in depigmentation in the placebo group (%CFB: +5·6). No significant reduction was seen with ritlecitinib 50 mg (+2·8) or 10 mg (+1·4%). Within stable lesions, ritlecitinib showed a statistically significant reduction in depigmentation extent, reflecting re-pigmentation [%CFB: 200/50 mg, −7·2 (P = 0·0045); 100/50 mg, −6·1 (P = 0·0082); 50 mg, −5·9 (P = 0·0134); 30 mg, −8·0 (P = 0·0092)] compared with the placebo group, where %CFB in de-pigmentation increased (%CFB: +0·5). No significant reduction was seen with ritlecitinib 10 mg (−3·3%). The magnitude of the re-pigmentation was numerically greater in stable lesions compared with that in active lesions. In patients with active NSV, ritlecitinib treatment for 24 weeks stabilized active lesions and promoted re-pigmentation of stable lesions.