Vitiligo Trial Assesses Ritlecitinib With nbUVB Under Modified Phototherapy Protocol
An analysis of a phase 2b clinical trial of ritlecitinib in patients with nonsegmental vitiligo (NSV) shows that the combination of the oral Janus kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) inhibitor with narrow-band ultraviolet B (nbUVB) phototherapy enhances skin repigmentation outcomes compared to ritlecitinib alone.
Ritlecitinib is approved for alopecia areata and is currently in late-stage development for NSV. Previous studies have shown that the agent effectively reduces CD3+/CD8+ T-cell infiltration and restores melanocyte markers in vitiligo lesions. The addition of nbUVB phototherapy—a treatment that stimulates melanocyte proliferation and migration—was hypothesized to further improve repigmentation outcomes.
The analysis, drawn from the extension phase of the randomized phase 2b trial (NCT03715829), evaluated patients aged 18 to 65 years with NSV involving at least 0.25% of facial body surface area. During the dose-ranging period of the study, patients were randomized to various doses of ritlecitinib or placebo for 24 weeks. Based on their response at week 16, patients were allocated to different treatment arms for the extension period, including ritlecitinib 200/50 mg monotherapy or the same regimen combined with narrow-band UVB (nbUVB) phototherapy twice weekly.
The nbUVB phototherapy protocol followed Vitiligo Working Group recommendations but was administered twice weekly instead of the usual 3 times per week, and patients were advised to avoid additional UV exposure outside the study protocol. Patients in the combination group who did not show at least a 10% improvement in Total Vitiligo Area Scoring Index by week 12 of the extension period were discontinued from treatment, following US Food and Drug Administration recommendations to minimize patient burden. This discontinuation rule applied only to the combination group and was informed by international treatment guidelines.
At 24 weeks, the combination therapy group (n = 43) showed numerically greater improvements in both facial and total body vitiligo scores compared to the ritlecitinib monotherapy group (n = 187). Specifically, the mean percentage change from baseline in Facial-Vitiligo Area Scoring Index (Facial-VASI) was −69.6% in the combination group versus −55.1% with ritlecitinib alone (observed case analysis; P = .009). Similarly, the mean reduction in Total-Vitiligo Area Scoring Index (Total-VASI) was −46.8% vs −24.5%, respectively (P < .001).
The combination regimen was well tolerated, and no new safety signals were identified. However, nine patients in the nbUVB group discontinued due to prespecified efficacy criteria requiring at least a 10% improvement in Total-VASI at week 12, a protocol criterion applied only to the combination group.
While these findings are exploratory and limited by the study’s small sample size and group-specific discontinuation rules, they suggest that adding nbUVB to ritlecitinib may enhance repigmentation outcomes in NSV. Investigators conclude that further studies are warranted to validate the additive or synergistic potential of this combined approach.
Reference
Yamaguchi Y, Peeva E, Adiri R, et al. Response to ritlecitinib with or without narrow-band ultraviolet B add-on therapy in patients with active nonsegmental vitiligo: results from a phase 2b extension study. J Am Acad Dermatol. 2025 Apr;92(4):781-789. doi:10.1016/j.jaad.2024.11.064
