Ritlecitinib in Nonsegmental Vitiligo: A Systematic Review and Comprehensive Program Synthesis of Clinical Efficacy, Safety, and Biomarker Outcomes

OBJECTIVE: To evaluate the clinical efficacy and safety of oral ritlecitinib, a selective Janus kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, for the treatment of nonsegmental vitiligo (NSV). DATA SOURCES: A systematic literature search was conducted across PubMed, Web of Science, Scopus, ClinicalTrials.gov, and the Cochrane Library from inception through August 31, 2026. Search terms included combinations of "ritlecitinib," "JAK inhibitor," and "vitiligo.." STUDY SELECTION AND DATA EXTRACTION: Included studies were clinical trials evaluating ritlecitinib, monotherapy, or with narrowband ultraviolet B (nbUVB), in adults with NSV. Five interrelated studies from the ritlecitinib phase 2b program involving 364 participants were identified for qualitative synthesis. Data extraction included study design, participant demographics, efficacy indices (F-VASI[Facial Vitiligo Area Scoring Index], T-VASI [Total Vitiligo Area Scoring Index], and PGIC-V [Patient Global Impression of Change-Vitiligo]), biomarker changes, and safety outcomes. Quality was assessed using the Cochrane Risk-of-Bias 2 tool. DATA SYNTHESIS: = .009) and total-body repigmentation. Darker skin phototypes (FST IV-VI) showed earlier and more robust responses (-37.4%) than lighter skin types (FST I-III; -15.2%). Safety outcomes were comparable with placebo, with overall adverse event rates between 60.0% and 86.2% and rare serious adverse events (≤2%). Biomarker analysis confirmed the downregulation of Th1-associated markers (CXCL9 and IFNG) and restoration of melanocyte markers like tyrosinase and Melan-A.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Ritlecitinib 50 mg daily provides a well-tolerated oral systemic option for active NSV. Efficacy is optimized when combined with nbUVB, and baseline skin phototype is a key predictor of the speed and extent of repigmentation. CONCLUSIONS: Oral ritlecitinib 50 mg daily is an effective systemic treatment for active NSV, demonstrating continuous repigmentation through 48 weeks with a favorable safety profile.