The following is a summary of “Improvements in immune/melanocyte biomarkers with JAK3/TEC family kinase inhibitor ritlecitinib in vitiligo,” published in the January 2024 issue of Allergy & Immunology by Guttman-Yassky, et al.
Vitiligo, an autoimmune depigmenting disorder lacking effective and safe treatments, remains incompletely understood in its pathogenesis. For a randomized, double-blind, placebo-controlled phase 2b trial, researchers sought to evaluate the effects of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on skin and blood biomarkers in individuals with nonsegmental vitiligo (NSV).
Sixty-five adults with NSV were enrolled in the substudy and received daily treatment for 24 weeks with either placebo (n = 14) or ritlecitinib at varying doses: 200 (with a loading dose)/50 mg (n = 13), 100/50 mg (n = 12), 50 mg (n = 11), 30 mg (n = 8), or 10 mg (n = 6). Skin biopsy samples (lesional and nonlesional) were collected at baseline and at 4 and 24 weeks. Changes in skin and blood molecular and cellular biomarkers were assessed using RNA sequencing, quantitative real-time PCR, proteomic analysis, and flow cytometry.
Ritlecitinib-treated groups exhibited downregulation of immune biomarkers and upregulation of melanocyte-related markers at weeks 4 and 24 compared to baseline and/or placebo. Significant reductions in CD3+/CD8+ T-cell infiltrates and significant increases in melanocyte markers (tyrosinase; Melan-A) were observed in NSV lesions in the 50 mg ritlecitinib groups (both P < .05). Dose-dependent downregulation was noted in T-cell activation, NK, cytotoxic, and regulatory markers in lesional skin (IL-2, IL2-RA, IL-15, CCR7, CD5, CRTAM, NCR1, XCL1, KIR3DL1, FASLG, KLRD; P < .05). TH
1 and TH2 markers were also downregulated in lesional skin and blood in a dose-dependent manner (P < .05). Changes in immune biomarkers correlated with clinical response.
Ritlecitinib led to significant downregulation of proinflammatory biomarkers and increased melanocyte products in the skin and blood of NSV participants, indicating its potential for treatment. Moreover, ritlecitinib-mediated changes positively correlated with clinical response.
Reference : jacionline.org/article/S0091-6749(23)01202-2/fulltext
