Light at the end of the tunnel for vitiligo therapy

There is a great need for novel therapies for vitiligo, as available treatment modalities have only shown limited efficacy. Promising results are now emerging for both a local and a systemic JAK inhibitor in this difficult-to-treat disease. Ruxolitinib cream showed long-term efficacy in 2 phase 3 trials with patients achieving substantial repigmentation, and the oral ritlecitinib showed efficacy over 48 weeks in a phase 2b trial.

The disease pathogenesis of vitiligo is largely regulated by IFN-γ activation and subsequent Janus kinase (JAK) signalling pathway, providing a rationale to target JAK proteins for this indication (see Box). The JAK1/JAK2 inhibitor ruxolitinib in a cream formulation has demonstrated substantial repigmentation over 52 weeks in a previous phase 2 trial [1]. In the 2 randomised, phase 3 studies TRuE-V1 (NCT04052425) and TRuE-V2 (NCT04057573), ruxolitinib cream was statistically superior to a vehicle in adolescents (≥12 years) and adult patients with non-segmental vitiligo at 24 weeks. “A key secondary endpoint was the development of the Face Vitiligo Area Scoring Index (F-VASI) over 52 weeks,” said Dr David Rosmarin (Tufts Medical Center, MA, USA) during the presentation of the long-term results [2]. The F-VASI measures the percentage of depigmented vitiligo skin expressed as a percentage of the total area of skin on the face (i.e. 100%).

After the 24-week, double-blind treatment phase, all vehicle participants were switched to ruxolitinib 1.5% cream, applied twice daily. Treatment efficacy continuously increased over time: about 75% of the participants who applied ruxolitinib cream from day 1 achieved an F-VASI 50 response, and approximately 75% of the participants achieved F-VASI 75 response by week 52. Almost a third of patients (30%) who applied the cream from day 1 achieved F-VASI 90 response by week 52. Dr Rosmarin pointed out that participants who crossed over from placebo also achieved very consistent results. “Repigmented areas match well with the normal skin,” he said. The cream was not only effective on the face but also on the body and the back of the hands, a difficult-to-treat area.

Ruxolitinib cream was well tolerated, with no clinically significant application site reactions or serious treatment-related adverse events. The question remains whether patients have to use the cream continuously. “We only have data from phase 2 trials to answer this question: some patients, particularly on lower doses of the cream, lost response; those with high doses retained response at month 3, but we probably need some kind of a maintenance therapy,” Dr Rosmarin said in the discussion.

Another oral option in the pipeline

Ritlecitinib is a novel JAK3/TEC inhibitor that might fill the therapeutic gap of an oral agent for vitiligo. It inhibits cytokines IL-15 and IFN-γ, which both play a pivotal role in the pathogenesis of the disease.

In a previous 2b trial, significant reductions in the centrally read F-VASI (crF-VASI) were noted in patients with non-segmental vitiligo. In the present phase 2b study, the efficacy of ritlecitinib was assessed in patients with non-segmental vitiligo across different Fitzpatrick skin types [3]. “Here, we only present those patients who received 50 mg in the dose-ranging period and 200 mg in the extension period,” explained Dr Yuji Yamaguchi (Pfizer, USA) during the presentation of the trial. The primary efficacy endpoint was the percentage change from baseline in the crF-VASI at week 48.

Of the study participants, 54.5% had Fitzpatrick skin Type I–III (n=145), and 45.5% Fitzpatrick skin Type IV–VI (n=121). In general, ritlecitinib was effective across all skin types. “But facial repigmentation is more pronounced in dark skin types,” Dr Yamaguchi said.

In the study, an ongoing and growing repigmentation was noted up to 48 weeks without a plateau of efficacy. At 48 weeks, crF-VASI score was reduced by 60% from baseline.

In general, ritlecitinib showed a favourable safety and tolerability profile in vitiligo patients across different Fitzpatrick skin types. As Dr Yamaguchi pointed out, therapy with the JAK3/TEC inhibitor led to surprisingly good cosmetic results across all skin types and repigmented areas blended in nicely with existing pigmented areas.

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   1. Rosmarin D, et al. Lancet 2020;396:110–120.
   2. Rosmarin D. Efficacy and safety of ruxolitinib cream monotherapy for the treatment of vitiligo: results from 2 52-week phase 3 studies. S026, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.
   3. Yamaguchi Y. Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, shows efficacy in patients with active non-segmental vitiligo across Fitzpatrick skin types: results from a Phase 2b, randomized, dose-ranging study with an extension period. S026, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.

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Posted on 17 May 202217 May 2024