Safety and efficacy of ruxolitinib cream for the treatment of vitiligo: A randomised controlled trial secondary analysis at 3 years

Vitiligo is a chronic autoimmune disease characterised by destruction of melanocytes resulting in patches of skin depigmentation1 that is associated with considerable disease burden.2, 3 Ruxolitinib (Janus kinase 1/2 inhibitor) cream4 demonstrated substantial repigmentation over 52 weeks and was well tolerated in a phase 2, dose-ranging, randomised study (NCT03099304) in adults (aged 18–75 years) with depigmentation of ≥0.5% and ≥3% of facial and nonfacial body surface area, respectively.5 Importantly, repigmentation was sustained over 104 weeks.6 We report additional safety and efficacy data from the study following 156 weeks of treatment and provide evidence of treatment durability 6 months after stopping treatment. Detailed study methodology for the double-blind, vehicle-controlled (through Week 24) and double-blind extension (through Week 52) periods has been published.5 After Week 52, all patients could apply 1.5% ruxolitinib cream twice daily (BID) during a 104-week open-label extension (OLE; Weeks 52–156), with 3–6 months' follow-up. During the OLE, patients with complete facial repigmentation could stop treatment or decrease application frequency based on investigator judgement; treatment could be restarted or application frequency increased if pigmentation was lost. Efficacy assessments included the percentage of patients achieving the following at Week 156: facial Vitiligo Area Scoring Index (F-VASI) improvements of ≥50%/≥75%/≥90% (F-VASI50/F-VASI75/F-VASI90); total Vitiligo Area Scoring Index (T-VASI) improvements of ≥50%/≥75% (T-VASI50/T-VASI75); facial Physician's Global Vitiligo Assessment (F-PhGVA) response (clear or almost clear skin); and Patient Global Impression of Change–Vitiligo (PaGIC-V) response (very much or much improved). Adverse event (AE) frequency and haematologic parameters were monitored. Of 77 patients initially randomised to the three highest doses of ruxolitinib cream (0.5% or 1.5% once daily, or 1.5% BID) who continued in the OLE, mean (SD) age was 51.2 (12.0) years, 57.1% (n = 44/77) were male, 87.0% (n = 67/77) were White, and 75.3% (n = 58/77) had Fitzpatrick skin types I–III. Baseline mean (SD) T-VASI and F-VASI scores were 18.7 (16.1) and 1.29 (0.78), respectively. The distribution of baseline disease characteristics was similar among patients initially randomised to 1.5% ruxolitinib cream BID and those continuing in the OLE. Twenty-five patients had Week 156 data. Among these, F-VASI50, F-VASI75, and F-VASI90 responses were achieved by 92.0% (n = 23/25), 68.0% (n = 17/25), and 48.0% (n = 12/25) of patients, respectively; T-VASI50 and T-VASI75 responses were achieved by 60.0% (n = 15/25) and 20.0% (n = 5/25), respectively. Additionally, F-PhGVA and PaGIC-V responses were achieved by 56.0% (n = 14/25) and 64.0% (n = 16/25), respectively. Across assessments, responses increased from Weeks 24 through 156; the most rapid improvements and the majority of responses were observed in the first 2 years (Table 1). These findings were consistent among the 33 patients randomised to 1.5% ruxolitinib cream BID on Day 1. Repigmentation of facial lesions was maintained for up to 6 months after stopping treatment in more than half of the small number of evaluable patients who applied ruxolitinib cream for >52 weeks (Table 1). Although one-third of patients were not evaluable at the 6-month follow-up visit after stopping treatment, F-VASI50 and F-VASI75 were maintained in 75% (n = 6/8) and 100% (n = 6/6) of evaluable patients, respectively; F-VASI90 was maintained in 64.7% (n = 11/17). Ruxolitinib cream was well tolerated over 3 years, with no significant safety signals observed or treatment-related serious AEs reported during the 104-week OLE, and no accumulation of AEs observed over 156 weeks. Treatment-emergent AEs occurred in 57.1% (n = 44/77) of patients in the OLE, the most common being sinusitis (5.2%, n = 4/77). The most common AE among patients who applied 1.5% ruxolitinib cream BID across the entire 3-year study was acne (18.2%, n = 6/33; all grade 1). During the OLE, one serious TEAE (grade 3 acute cholecystitis) was reported in a patient applying 1.5% ruxolitinib cream BID from Day 1, which was considered non–treatment-related by investigators. In total, 9.1% (n = 7/77) had treatment-related AEs (all grades 1–2). No clinically relevant changes in haemoglobin or platelet levels were observed over 156 weeks, regardless of ruxolitinib cream strength at initial randomisation. These results add to previously reported efficacy and safety data with ruxolitinib cream, which demonstrated substantial and continuous repigmentation of vitiligo lesions as well as consistent safety profiles after treatment of up to 1 year in both phase 2 and 3 studies.5, 7 We conclude that ruxolitinib cream produced substantial facial and total body repigmentation of vitiligo lesions and was well tolerated through 3 years of treatment. Facial lesion repigmentation improvements of ≥50% were maintained for up to 6 months among approximately three-quarters of evaluable patients after stopping treatment. Larger studies are needed to confirm these findings; nonetheless, these data support the long-term safety and efficacy of ruxolitinib cream for the treatment of vitiligo. We would like to thank the patients, investigators, and investigational sites whose participation made this 3-year study possible. This study was funded by Incyte Corporation (Wilmington, DE, USA). Writing assistance was provided by Samantha Locke, PhD, an employee of ICON (Blue Bell, PA, USA), and was funded by Incyte. JEH has served as a consultant for AbbVie, Aclaris Therapeutics, BiologicsMD, EMD Serono, Genzyme/Sanofi, Janssen, Pfizer, Rheos Medicines, Sun Pharmaceuticals, TeVido BioDevices, The Expert Institute, 3rd Rock Ventures, and Villaris Therapeutics; has served as an investigator for Aclaris Therapeutics, Celgene, Dermira, EMD Serono, Genzyme/Sanofi, Incyte Corporation, LEO Pharma, Pfizer, Rheos Medicines, Stiefel/GlaxoSmithKline, Sun Pharmaceuticals, TeVido BioDevices, and Villaris Therapeutics; holds equity in Aldena Therapeutics, NIRA Biosciences, Rheos Medicines, TeVido BioDevices, and Villaris Therapeutics; is a scientific founder of Aldena Therapeutics, NIRA Biosciences, and Villaris Therapeutics; and has patents pending for IL-15 blockade for treatment of vitiligo, JAK inhibition with light therapy for vitiligo, and CXCR3 antibody depletion for treatment of vitiligo. AGP has served as an investigator for Aclaris Therapeutics, Immune Tolerance Network, Incyte, and Pfizer; a consultant for AbbVie, Arcutis, Avita Medical, Chromaderm, Immune Tolerance Network, Incyte, Pfizer, TWi, Viela Bio, and Villaris; and holds stock options for Tara Medical and Zerigo Health. ML is an employee of Mount Sinai Hospital, which receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research and is a consultant for Aditum Bio, Almirall, AnaptysBio, Arcutis, Aristea, Arrive Technology, Avotres Therapeutics, BioMX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr. Reddy's Laboratories, Evelo, Evommune, Facilitate International Dermatologic Education, Forte, Foundation for Research and Education in Dermatology, Helsinn, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, and Verrica. IHH has served as an advisory board member for AbbVie; a consultant for Boehringer Ingelheim, Galderma Laboratories LP, Incyte, Pfizer, and UCB; a principal investigator for Avita, Bayer, Estée Lauder, Ferndale Laboratories, Incyte, Lenicura, L'Oréal, Pfizer, and Unigen; immediate past president of the HS Foundation; and a board member of the Global Vitiligo Foundation. PG has served as a consultant for Aclaris Therapeutics, Clarify Medical, DermaForce, Incyte, Proctor data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review formal analysis (equal); validation (lead); writing – review data curation (equal); formal analysis (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); methodology (equal); writing – review data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); writing – review July 5–7, 2022). 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