Vitiligo: Oral JAK1 inhibitor induces increasing repigmentation over time

Continuing povorcitinib treatment after a 6-month double-blind phase led to additional repigmentation for many participants of a vitiligo phase 2b trial.

Change in T-VASI was significantly higher over placebo, at week 24

The JAK1 inhibitor povorcitinib was tested as a treatment for non-segmental vitiligo in a phase 2b trial (NCT04818346) that enrolled 171 participants1. In 4 equally powered study arms, the participants were treated with 3 different dosages of povorcitinib (i.e. 15 mg, 45 mg, 75 mg) or placebo once daily over 24 weeks. Thereafter, all participants starting on this regimen were continued on 45 mg, and all other participants received 75 mg of the study drug for 28 more weeks, which was followed by 6 months of off-treatment follow-up.

The median age of participants was 50 years, and 54.4% were women. Vitiligo was diagnosed at a mean of 19.4 years earlier. At week 24, the change in total body (T) Vitiligo Area Scoring Index (VASI) was significantly higher in all povorcitinib groups than on placebo with least square mean depigmentation improvements of 19.1%, 17.8% and 15.7% (15 mg, 45 mg, and 75 mg) compared with -2.3% on placebo (P<0.01 for all comparisons to placebo).

Up to week 52, these results further advanced to 42.7% and 41.3% in those who were on 45 mg and 75 mg povorcitinib from the start. “Even at week 52, we haven’t reached the plateau; this is something very interesting,” Prof. Khaled Ezzedine (University Paris-Est Créteil, France) pointed out. T-VASI50 was achieved by 15.2% on 45 mg after 6 months and 37.0% at week 52.

Maintained durability response is observed, although sample was small

With regard to facial (F) VASI, statistical significance was also present in all regimens of povorcitinib, with the highest rate on continued 45 mg from day 1: 36.4% versus 5.1% (P<0.0001 vs placebo) at week 24 and 63.8% after 1 year. F-VASI75 was observed in 45.5–58.6% at the end of the extension period. Prof. Ezzedine also explained that although the sample size for the period without treatment from weeks 52–76 was too small for statistical analysis, the results suggested a maintained durability of response in T-VASI and F-VASI.

As for safety up to week 52, the overall rate of treatment-emergent adverse events on povorcitinib was reported at 89.3%, ≥grade 3 at 16.9%, and serious at 2.4%. “No serious adverse events were considered related to the treatment, and no new safety signals were observed,” Prof. Ezzedine commented, adding that povorcitinib was generally well-tolerated at all doses.

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  1. Ezzedine K. Efficacy and safety of povorcitinib for extensive vitiligo: 52-week results from a double-blinded, placebo-controlled, dose-ranging phase 2b study. D1T01.1A, EADV Congress 2023, 11–14 October, Berlin, Germany.