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Introduction/Background Vitiligo is a chronic autoimmune disease characterized by melanocyte destruction, leading to skin depigmentation. Limited data are available regarding the efficacy of long-term topical vitiligo treatment. In 2 randomized, double-blinded, vehicle-controlled phase 3 studies in adults and adolescents (aged ≥12 y) with nonsegmental vitiligo (TRuE-V1 [NCT04052425]; TRuE-V2 [NCT04057573]), ruxolitinib cream application resulted in statistically superior improvements in repigmentation versus vehicle in the primary and all key secondary endpoints at Week 24 and was well tolerated. In the open-label period of TRuE-V1/TRuE-V2 (Weeks 24-52) and the TRuE-V long-term extension (LTE; Weeks 52-104) study (NCT04530344), further improvements in facial and body repigmentation (as assessed by Vitiligo Area Scoring Index [VASI] responses) were observed through Week 104 among patients who continued to apply ruxolitinib cream. Objectives: In this pooled analysis, we evaluated shifts in facial and total body VASI (F-VASI/T-VASI) responses among patients with vitiligo who had limited or no repigmentation at Week 24 and who continued to apply ruxolitinib cream for an additional 80 weeks. Methods: In TRuE-V1/TRuE-V2, patients were randomized 2:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through Week 52. Patients who completed TRuE-V1/TRuE-V2 were eligible to enroll in the TRuE-V LTE. Patients who did not achieve ≥90% improvement in F-VASI at Week 52 continued to apply open-label 1.5% ruxolitinib cream until Week 104. Patients initially randomized to apply ruxolitinib cream who had <25% improvement from baseline in F-VASI or T-VASI at Week 24 and had non-missing VASI assessments at the evaluated time points were included in this analysis. Shifts in F-VASI and T-VASI were assessed among patients with no facial/body repigmentation or worsening depigmentation (≤0% improvement in F-VASI/T-VASI) and patients with limited facial/body repigmentation (>0%- <25% improvement in F-VASI/T-VASI) at Week 24. Results: Among patients with no facial repigmentation at Week 24, improvements in F-VASI at Weeks 52 and 104 were observed in 77.8% (49/63) and 97.1% (34/35) of patients, respectively. Among patients with limited facial repigmentation at Week 24, F-VASI improvements at Weeks 52 and 104 were observed in 64.0% (32/50) and 83.3% (30/36) of patients, respectively. Across both groups, 54.9% (39/71) of patients achieved =75% improvement from baseline in F-VASI (F-VASI75) at Week 104. Among those with no body repigmentation at Week 24, T-VASI improvements at Weeks 52 and 104 were observed in 79.6% (39/49) and 93.3% (28/30) of patients, respectively. For those with limited body repigmentation at Week 24, T-VASI improvements at Weeks 52 and 104 were observed in 64.5% (80/124) and 81.6% (62/76) of patients, respectively. Across both groups who had <25% improvement in total body repigmentation at Week 24, 50.0% (53/106) of patients achieved ≥50% improvement in T-VASI (T-VASI50) at Week 104. Conclusions: In the TRuE-V studies, ruxolitinib cream application for an additional 80 weeks resulted in improved repigmentation among patients with nonsegmental vitiligo who had limited or no repigmentation at Week 24. These 2-year TRuE-V results highlight the importance of prolonged treatment in patients with vitiligo, even when minimal or no repigmentation is achieved after 6 months of treatment. [ABSTRACT FROM AUTHOR]

Introduction & Objectives: Janus kinase (JAK) inhibition is a promising approach for the treatment of vitiligo. Here, we report the clinical efficacy and safety of upadacitinib (UPA), an oral JAK inhibitor, in a phase 2b multicenter, randomized, double-blind, placebo-controlled study of adults with extensive non-segmental vitiligo (NSV). Materials & Methods: Eligible patients were aged 18-65 years with NSV, a Facial Vitiligo Area Scoring Index (F-VASI) of ≥0.5, and a Total Vitiligo Area Scoring Index (T-VASI) of ≥5 at baseline. This 52-week study (NCT04927975) comprised 2 periods. In period 1, patients were randomly assigned to once daily UPA 22 mg (UPA22), UPA 11 mg (UPA11), UPA 6 mg (UPA6), or placebo (PBO) for 24 weeks of treatment. In a 28-week blinded extension (period 2), patients receiving UPA during period 1 continued their respective regimens; patients who received PBO in period 1 were pre-assigned to either UPA11 or UPA22. Clinical efficacy endpoints evaluated through week 36 included percent change from baseline (%CFB) in F-VASI (week 24, primary endpoint), reductions from baseline in F-VASI of ≥50% (F-VASI 50) and ≥75% (F-VASI 75), %CFB in T-VASI, and reduction from baseline in T-VASI of ≥50% (T-VASI 50). Safety data as of January 13, 2023 (data cutoff date) are presented. Results: Of the 185 patients enrolled in period 1, 165 (89.2%) continued to period 2. At baseline, 68% of patients had extensive vitiligo (T-VASI > 10), and 71% had active vitiligo. At week 24, the %CFB in F-VASI was greater with UPA11 (-35.6%) and UPA22 (-34.0%) vs PBO (-14.4%; nominal P = .005 and P = .013, respectively). A greater proportion of patients achieved F-VASI 50 and F-VASI 75 with UPA11 (38.3%, 19.1%) and UPA22 (39.5%, 14.0%) vs PBO (10.9%, 2.2%; nominal P < .05 for both doses and for both endpoints). Likewise, the %CFB in T-VASI was greater with UPA11 (-17.3%) and UPA22 (-20.7%) vs PBO (-6.4%; nominal P = .026 and P = .005, respectively). A higher percentage of patients achieved T-VASI 50 with UPA22 (11.6%) than with PBO (2.2%; nominal P = .027). UPA efficacy continued to improve through week 36, with %CFB in F-VASI for UPA6, UPA11, and UPA22 of -20.8%, -44.9% and -47.7%, respectively. At week 36, F-VASI 50 was achieved with UPA6, UPA11, and UPA22 by 34.2%, 54.3% and 61.5% of patients and F-VASI 75 by 15.8%, 40.0%, and 30.8%, respectively. At week 36, %CFB in T-VASI for UPA6, UPA11 and UPA22 were -24.3%, -32.0% and -37.6%, with 10.5%, 20.0% and 19.2% of patients, respectively, achieving T-VASI 50. Treatment-emergent adverse event (TEAE) rates were generally similar with UPA and PBO in period 1 (most common TEAEs: COVID-19, acne, fatigue, and headache) and were similar across treatment arms in period 2. One death adjudicated as undetermined/unknown cause and deemed by the investigator to have no reasonable possibility of being related to study drug occurred in the UPA22 group (period 1). One adjudicated event of nonfatal ischemic stroke occurred with UPA11 (period 2). There were no adjudicated events of venous thromboembolism, gastrointestinal perforation, or events of opportunistic infection, active tuberculosis, or malignancy. Conclusion: Treatment with UPA for 24 weeks resulted in greater improvements vs PBO in the clinical outcomes of adults with extensive NSV. Observed clinical efficacy continued to improve through week 36 with UPA treatment. UPA was generally well tolerated, with no new safety signals identified. [ABSTRACT FROM AUTHOR]