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For patients with active nonsegmental vitiligo, treatment often requires a multifaceted approach to achieve meaningful repigmentation. In a recently published phase 2b extension study, adding narrow-band ultraviolet B (nbUVB) phototherapy to ritlecitinib, an oral Janus kinase (JAK) 3/tyrosine-protein kinase inhibitor, resulted in significantly greater repigmentation than ritlecitinib alone in patients with nonsegmental vitiligo over 24 weeks.

The goal of the study, published in the Journal of the American Academy of Dermatology, was to evaluate the efficacy and tolerability of ritlecitinib in combination with nbUVB in adult patients with active nonsegmental vitiligo over a 24-week treatment period. The authors included researchers from Mount Sinai in New York City; Henry Ford Hospital in Detroit, Michigan; Hôpital Henri Mondor in Créteil, France; and Pfizer, the manufacturer of ritlecitinib, which is currently approved for alopecia areata and is under investigation for vitiligo and other autoimmune conditions.

Enhanced Repigmentation With Combination Therapy 

The trial enrolled 230 adults with active nonsegmental vitiligo who were previously part of a 24-week, randomized, double-blind, placebo-controlled, dose-ranging study of ritlecitinib. Participants were randomly assigned to receive either ritlecitinib alone (200 mg daily for 4 weeks, then 50 mg daily for 20 weeks) or ritlecitinib combined with nbUVB phototherapy twice weekly for 12 weeks. Efficacy was evaluated using changes in Facial and Total Vitiligo Area Scoring Index (F-VASI and T-VASI) scores, along with patient-reported outcomes.

By week 24, the combination of ritlecitinib plus nbUVB was associated with significantly greater repigmentation than ritlecitinib monotherapy. In observed case analyses, the mean improvement in F-VASI was 69.6% in the combination group vs 55.1% with monotherapy (P = .009). For total body repigmentation, T-VASI improved by 46.8% in the combination group vs 24.5% in the monotherapy group (P < .001).

“The additive effect of nbUVB on repigmentation with ritlecitinib was more evident with T-VASI than F-VASI,” the authors wrote, “indicating that non–sun-exposed skin may be more sensitive to the additive effects of nbUVB on ritlecitinib than sun-exposed skin in promoting repigmentation in patients with vitiligo.”

The benefits were particularly notable in patients with more extensive facial involvement at baseline (≥ 0.5% facial body surface area). In this subgroup, 80.0% of patients receiving combination therapy achieved at least 75% improvement in facial repigmentation compared with 32.4% in the monotherapy group (P = .007). This suggested that those with more extensive vitiligo may respond more favorably to treatment compared with patients with limited skin involvement, according to the authors.

Patient Experience and Safety Outcomes 

The Patient Global Impression of Change–Vitiligo questionnaire, which asked patients to rate their overall improvement, mirrored the objective results. In the combination therapy group, 57.7% of patients reported feeling “much improved” or “very much improved” compared with 30.0% of patients in the monotherapy group (P = .012).

The safety profile of ritlecitinib, with or without nbUVB, was consistent with those reported in the previous dose-ranging study and was thought to be well-tolerated over 24 weeks, according to the authors. Treatment-emergent adverse events occurred in 74.4% of patients receiving ritlecitinib plus nbUVB and 63.6% receiving ritlecitinib alone.

Complementary Mechanism of Action

The authors proposed that the additive benefit of nbUVB may stem from its ability to stimulate melanocyte proliferation and migration, complementing ritlecitinib’s immunomodulatory role in halting melanocyte destruction.

“This is consistent with several small studies demonstrating positive results with the combination of phototherapy and JAK inhibition in patients with vitiligo,” the authors wrote, referencing findings from a 2022 meta-analysis.

While the duration of nbUVB exposure in the study (12 weeks) was relatively short, especially compared with real-world use, significant repigmentation was still observed in many patients, the authors reported.

Home-Based Phototherapy Could Expand Access 

Emma Guttman-Yassky, MD, PhD, professor and system chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City and a study co-author, emphasized the clinical relevance of the findings.

“This is an important publication, as it shows that JAK inhibitors work even alone in repigmentation, without the need for adding phototherapy,” she told Medscape Medical News. “If we add phototherapy, it has an adjuvant effect, and we can increase responses.”

Guttman-Yassky noted that the findings offer clinicians flexibility in tailoring treatment to their patients’ access and preferences. “This has great implications for clinicians, as it gives flexibility that depends on the availability of phototherapy,” she added. “It also implies that potentially home units for phototherapy may work as well, and patients can have the phototherapy done together with the JAK inhibitors in their own homes. This will maximize treatment responses in vitiligo.”

She acknowledged that phototherapy access remains a limitation in some areas but maintained that the potential for home-based devices makes this a feasible and promising approach. “Ideally a doctor’s office may be better, but this is not always feasible,” she said.

Limitations 

This is the first phase 2b trial to prospectively evaluate the combination using both objective and patient-reported measures. As an exploratory extension analysis, the study was not designed to directly compare treatment arms, and the group sizes were unequal (187 vs 43). Additionally, the mandated discontinuation for early nonresponse in the combination group, but not in the monotherapy group, introduced potential bias in the observed case data, the authors noted.

The study was funded by Pfizer. The lead author, Yuji Yamaguchi, MD, PhD, an executive director of Clinical Research at Pfizer, and four other authors reported equity in Pfizer. Three authors reported receiving consulting fees and serving as investigators for Pfizer, and another author reported serving as past president of the Global Vitiligo Foundation. Guttman-Yassky reported serving as an advisory board member for Pfizer, Asana BioSciences, Celgene, Dermira, Galderma, Glenmark, MedImmune, Novartis, Regeneron, Sanofi, Stiefel/GlaxoSmithKline, and Vitae (honorarium); receiving consulting fees from Pfizer, AbbVie, Almirall, Anacor, Asana BioSciences, Celgene, Dermira, Galderma, Eli Lilly and Company, Glenmark, Kyowa Kirin, LEO Pharma, MedImmune, Mitsubishi Tanabe Pharma Corporation, Novartis, Regeneron, Sanofi, Stiefel/GlaxoSmithKline, and Vitae (honorarium); and serving as an investigator for Celgene, Eli Lilly and Company, LEO Pharma, MedImmune, and Regeneron (grants to institution). 

Jennifer Fisher is a Connecticut-based dermatology physician associate and freelance medical writer.