Efficacy and safety of ruxolitinib cream for the treatment of vitiligo by patient demographics and baseline clinical characteristics: Week 52 pooled subgroup analysis from two randomized phase 3 studies

Abstract

Abstract Vitiligo is a chronic autoimmune disease that targets melanocytes, causing skin depigmentation. Disease pathogenesis is largely regulated by interferon-γ activation of the Janus kinase (JAK) signalling pathway. A cream formulation of the JAK1/JAK2 inhibitor ruxolitinib demonstrated substantial re-pigmentation in two randomized, double-blind, vehicle-controlled phase 3 studies of adults and adolescents with vitiligo (TruE-V1 and TruE-V2). Pooled 52-week efficacy and safety data based on baseline demographics and clinical characteristics from the TruE-V studies are analysed and reported here. TruE-V1 (NCT04052425) and TruE-V2 (NCT04057573) were conducted in North America and Europe. Patients ≥ 12 years old diagnosed with nonsegmental vitiligo (NSV) with depigmentation covering ≤ 10% total body surface area (BSA), including facial and total Vitiligo Area Scoring Index (F-VASI/T-VASI) scores ≥ 0·5/≥ 3, were eligible for enrolment. Patients were randomized 2 : 1 to twice-daily 1·5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1·5% ruxolitinib cream through Week 52 (open-label extension). At Week 52, patients who achieved ≥ 75% improvement from baseline in F-VASI (F-VASI75) were evaluated by sex, age group, Fitzpatrick skin type, facial BSA (F-BSA), investigator-assessed disease stability and previous therapy. Safety and tolerability were also assessed. Week 52 data are reported as observed. In total, 674 patients were randomized in the TRuE-V studies (ruxolitinib cream, n = 450; vehicle, n = 224); 673 and 661 patients were included in the safety and efficacy analyses, respectively, and 569 patients continued in the open-label extension (ruxolitinib cream from Day 1, n = 385; crossover from vehicle, n = 184). Mean (SD) age at baseline was 39·5 (15·1) years, and 27·9% of patients had Fitzpatrick skin types IV–VI. Baseline mean F-VASI and T-VASI values were 0·92 and 6·69, respectively. At Week 52, 50·3% of patients who applied ruxolitinib cream from Day 1 achieved F-VASI75. Efficacy by F-VASI75 response was identified in all demographic and clinical characteristic subgroups. Substantive F-VASI75 responses were seen for men [(n = 149), 43·6%] and women [(n = 201), 55·2%], and all age groups [12–17 years (n = 50), 48·0%; 18–64 years (n = 275), 52·0%; ≥ 65 years (n = 25), 36·0%]. F-VASI75 responses were also generally consistent based on skin type [I–III (n = 249), 47·4%; IV–VI (n = 101), 57·4%], F-BSA [<1·5% (n = 283), 49·1%; ≥ 1·5% (n = 67), 55·2%], investigator-assessed disease stability [stable (n = 257), 49·4%; progressive (n = 93), 52·7%] and previous therapy [topical corticosteroids (n = 110), 50·9%; topical calcineurin inhibitors (n = 126), 49·2%; phototherapy (n = 113), 54·0%]. Treatment-related adverse events (AEs) occurred in 13·7% of patients who applied ruxolitinib cream at any time during the study, with generally similar rates among demographic subgroups for patients who applied ruxolitinib cream. Adolescent and adult patients with NSV applying ruxolitinib cream achieved efficacy per F-VASI75 at Week 52 regardless of baseline demographics or clinical characteristics. Ruxolitinib cream was well tolerated, and the incidence of treatment-related AEs was similar across subgroups.