The chronic autoimmune disease vitiligo has an adverse effect on the quality of life. Current treatment modalities are limited and only insufficiently efficacious. Ritlecitinib is a selective inhibitor of JAK3 and the TEC kinase family. Preclinical data has shown inhibition of the cytolytic function of CD8+ T cells and natural killer cells that might be beneficial in inflammatory diseasessuch as vitiligo1.
Prof. Khaled Ezzedine (University Hospital Henri Mondor, France) reported the primary endpoint results of the double-blind, randomised, placebo-controlled, 24-week period of a phase 2b study (NCT03715829) of ritlecitinib in patients with active non-segmental vitiligo2. The first 24 weeks of the study was a dose-ranging phase in which 5 doses of the JAK3 inhibitor were tested (from 10 to 50 mg). In the following maintenance phase all patients will be treated with 50 mg ritlecitinib. The results of a 24-week extension period will be presented later this year.
The primary endpoint was the change from baseline in the Vitiligo Area Scoring Index in the face (F-VASI) at week 24. In addition, a couple of secondary endpoints were assessed, such as the proportion of patients achieving ≥75% improvement in the F-VASI and safety and tolerability. A total of 364 patients were treated, 68% of them Caucasian.
At week 24, ritlecitinib in the highest dose of 50 mg daily with or without induction (100 mg or 200 mg daily for 4 weeks) met the primary endpoint. The percentage change from baseline ranged from -21 to -23 in the F-VASI among these 3 dose groups. Moreover, 75% improvement in F-VASI ranged from 8 to 12% in these groups (P<0.05 for each group). “We noticed that the treatment effect was much larger during the following extension period than in the dose-ranging period,” Prof. Ezzedine said. At week 48, around 30% of participants achieved a F-VASI 75 response. percentage change from baseline in F-VASI ranged from -60 to -66.
The high efficacy also showed in the patient´s perception: the proportion of patients who were “much improved” or “very much improved” in the patient global impression of change scale increased from week 24 to week 48 in all treatment sequences with a range from 10.7% to 57.9%.
A total of 756 adverse events were observed. The proportion was similar across treatment groups. Treatment was discontinued by 19 participants. The numbers were similar across the treatment groups and not dose dependant. Prof. Ezzedine concluded that ritlecitinib was effective and well-tolerated in patients with vitiligo who received continuous treatment for up to 48 weeks.