Efficacy and safety of ritlecitinib in vitiligo patients across Fitzpatrick skin types with biomarker analyses

Abstract Efficacy and safety of ritlecitinib (an oral JAK3/TEC family kinase inhibitor) were evaluated in patients with nonsegmental vitiligo (NSV) across Fitzpatrick skin types (FSTs). Patients with FST I‐III (‘light skin’; n = 247) and FST IV‐VI (‘dark skin’; n = 117) received once‐daily ritlecitinib 50 mg (with/without 4‐week loading dose), low‐dose ritlecitinib or placebo for 24 weeks. At baseline, patients with light skin displayed higher CLM‐1 and NCR1 serum levels than patients with dark skin ( p < 0.05). At 24 weeks, ritlecitinib 50 mg improved the extent of depigmentation measured by percent change from baseline in facial‐vitiligo area scoring index (placebo‐adjusted mean difference [90% CI]) in patients with light (−15.2 [−24.7, −5.8]; p = 0.004) and dark (−37.4 [−50.3, −24.4]; p < 0.0001) skin, with continuous re‐pigmentation through week 48. Treatment‐emergent adverse events were similar across FSTs. At weeks 4 and 24, ritlecitinib 50 mg reduced CXCL11 serum levels ( p < 0.001) in patients with light skin, whereas patients with dark skin had increased levels at week 4 ( p = 0.05) and no significant change at week 24. Ritlecitinib 50 mg decreased IL‐9 and IL‐22 expression levels in dark skin compared with light skin (qPCR; p < 0.05). These differences in immune dysregulations may explain why NSV patients with dark skin respond to therapy earlier than patients with light skin.