Ritlecitinib Efficacious for Non-Segmental Vitiligo Across Various Subgroups

Ritlecitinib is effective across various subgroups of patients with non-segmental vitiligo up to 48 weeks, new findings suggest.1

This drug was evaluated in a recent study authored by investigators such as Yuji Yamaguchi, the Executive Director of Clinical Research at Pfizer. Yamaguchi and colleagues highlighted ritlecitinib’s use as an oral, selective, dual inhibitor of JAK3 and the TEC family kinases.

The drug is currently under phase 3 investigation for its use in treating non-segmental vitiligo. Prior research noted by the investigators points to ritlecitinib’s demonstrated efficacy and safety in a phase 2b analysis.2

“...[Data] are limited on how other demographic and clinical characteristics affect the efficacy of ritlecitinib in patients with NSV,” the investigative team wrote.1 “This post hoc analysis explored the efficacy of ritlecitinib in patients with NSV stratified by baseline demographic and clinical characteristics.”

Study Design Details

Previous information reported in a phase 2b clinical study was used in this post hoc evaluation (NCT03715829). This trial had looked at treatment with ritlecitinib among adult patients living with active non-segmental vitiligo. The study had consisted of a 24-week dose-ranging phase, a period then followed by a 24-week extension phase. Those between the ages of 18 - 65 years of age were deemed eligible, provided they had active non-segmental vitiligo.

The presence of patient disease was defined by the observation of at least a single active vitiligo-related lesion. In terms of activity criteria, examples included newly appearing or enlarging lesions within the prior 3 months and/or confetti-like, trichrome, or Koebner lesions. Yamaguchi et al did not include historical isomorphic reactions.

All of those involved as participants were also required to have facial involvement of their vitiligo, with the disease affecting .25% of body surface area (BSA) at minimum. In the study’s initial 24-week dose-ranging period, those evaluated were treated with a maintenance dose of ritlecitinib at 50 mg once-per-day. The drug was administered either alone or after the conclusion of a 4-week loading regimen of 200 mg or 100 mg, taking place once daily.

Within the investigators’ subsequent extension period, trial subjects at Week 16 who had not succeeded in attaining at least an improvement of 50% from the point of baseline in their Total Vitiligo Area Scoring Index (T-VASI) were shifted to 1 of several different potential treatment strategies. These strategies would include open-label ritlecitinib 200/50 mg combined with narrowband UVB phototherapy, open-label brepocitinib, or blinded ritlecitinib on a 200/50 mg dosing regimen.

In Yamaguchi and coauthors’ present analysis, they focused on individuals featured in the extension phase who were randomized to the blinded ritlecitinib 200/50 mg arm of the study. In this particular cohort, trial participants were given a 200-mg loading dose over 4 weeks followed by 50 mg on a once-per-day regimen. Efficacy of ritlecitinib’s use was assessed by the investigators through a determination of the percentage of individuals attaining at least a 75% improvement from the point of baseline on their centrally read Facial Vitiligo Area Scoring Index (F-VASI75) score at the 24 and 48-week marks. Outcomes were then further evaluated across baseline demographic and clinical subgroups.

Findings on Ritlecitinib in Non-Segmental Vitiligo

There were 184 patients in total from the dose-ranging phase and 90 individuals from the extension phase who Yamaguchi and colleagues involved in their post hoc analysis. The proportion of those showing a F-VASI75 score was 8.7% at 24 weeks and rose to 26.7% by the 48-week mark. The investigative team noted, across all of the subgroups of patients with non-segmental vitiligo, ritlecitinib demonstrated clinically meaningful levels of facial re-pigmentation.

By the 24-week mark, the team highlighted numerical but statistically non-significant differences in subjects’ responses, specifically among certain subgroups. Yamaguchi et al observed increased rates of disease response among men versus women. These greater rates were also observed in individuals with Fitzpatrick skin types III–VI as opposed to I–II.

Other subgroups in this category were those with facial BSA involvement of at least 0.5% versus less than 0.5%, patients without leukotrichia versus those with leukotrichia, and treatment-naïve individuals versus those previously given treatment. These subgroup differences were noted by the team as less apparent by the 48-week mark.

By the extension period’s conclusion, there remained only modest, non-significant trends. These data favored patients with a body mass index of 30 kg/m² or lower, individuals without leukotrichia, and those without comorbid conditions. There were no notable distinctions detected by the investigative team across the remaining baseline characteristics.

“Overall, ritlecitinib was efficacious across different patient subgroups up to 48 weeks,” the team concluded.1 “These findings contribute to the understanding of how demographic and clinical characteristics affect clinical response to ritlecitinib in patients with active vitiligo, potentially guiding more personalized therapeutic approaches and improving patient outcomes.”

References

1. Pandya AG, Hamzavi I, Yamaguchi Y, et al. Efficacy of Ritlecitinib for Vitiligo Treatment Stratified by Baseline Demographic and Clinical Characteristics: Post Hoc Analysis of a Phase 2b Study. JEADV Clinical Practice. https://doi.org/10.1002/jvc2.70193.

2. Ezzedine K, Peeva E, King B, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial. J Am Acad Dermatol. 2023 Feb;88(2):395-403. doi: 10.1016/j.jaad.2022.11.005. Epub 2022 Nov 9. Erratum in: J Am Acad Dermatol. 2023 Sep;89(3):639. doi: 10.1016/j.jaad.2023.04.001. PMID: 36370907.