Efficacy of ruxolitinib cream in vitiligo by patient characteristics and affected body areas: Descriptive subgroup analyses from a phase 2, randomized, double-blind trial
Authors: Iltefat Hamzavi, David Rosmarin, John E. Harris, Amit G. Pandya, Mark Lebwohl, Alice B. Gottlieb, Kathleen Butler, Fiona I. Kuo, Kang Sun, Pearl Grimes
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: Vitiligo is a chronic autoimmune disease resulting in patches of depigmented skin1Taïeb A. Picardo M. Clinical practice. Vitiligo.N Engl J Med. 2009; 360: 160-169Crossref PubMed Scopus (281) Google Scholar and reduced quality of life.2Morrison B. Burden-Teh E. Batchelor J.M. Mead E. Grindlay D. Ratib S. Quality of life in people with vitiligo: a systematic review and meta-analysis.Br J Dermatol. 2017; 177: e338-e339Crossref PubMed Scopus (17) Google Scholar In a randomized, dose-ranging phase 2 study (NCT03099304) in 157 adult patients, the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib cream produced substantial repigmentation of facial and total body vitiligo lesions after 24 weeks, with continued improvement through week 52, and was well tolerated.3Rosmarin D. Pandya A.G. Lebwohl M. et al.Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial.Lancet. 2020; 396: 110-120Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar Here, we present treatment response subanalyses from the phase 2 trial. The proportion of patients receiving 1.5% ruxolitinib cream twice daily who achieved ≥50% improvement in facial Vitiligo Area Scoring Index (F-VASI50) at week 24 was assessed by demographics and baseline clinical characteristics. Additionally, the proportion of patients initially randomized to 1.5% ruxolitinib cream once daily or twice daily who achieved ≥50% and ≥75% improvement from baseline in total VASI (T-VASI50 and T-VASI75, respectively) at week 52 was assessed by affected body area. Because the ruxolitinib cream application was limited to ≤20% of total body surface area (T-BSA; the limit for the practicality of application), total body analyses were conducted only in patients with vitiligo affecting ≤20% of T-BSA at baseline. Data were analyzed using descriptive statistics. Among the 33 patients who received 1.5% ruxolitinib cream twice daily, a larger proportion of F-VASI50 responders at 24 weeks were aged ≤50 years compared with >50 years (58.8% vs 31.3%; Fig 1). A larger proportion of women versus men (60.0% vs 33.3%) were F-VASI50 responders. A larger proportion of responders had ≤1.5% affected baseline facial BSA, disease duration >20 years, and previous treatment with phototherapy. There were no substantial differences between responders based on race, skin type, baseline T-BSA, or disease status. Among patients with vitiligo affecting ≤20% of T-BSA at baseline, both doses of ruxolitinib cream (1.5% once daily and twice daily) produced notable T-VASI50 and T-VASI75 responses at week 52 (Table I). The 1.5% ruxolitinib cream twice-daily dose produced the highest proportion of T-VASI50 responders in the head/neck region (60.0%), followed by the upper and lower extremities (52.9% and 52.6%, respectively). T-VASI50 of the hands and feet was noted for 15.0% and 29.4% of patients, respectively, who received 1.5% ruxolitinib cream twice daily.Table IProportion of patients who applied 1.5% ruxolitinib cream and achieved T-VASI50 or T-VASI75 responses at week 52∗T-VASI50 and T-VASI75 responses are reported for the subset of patients with baseline T-BSA ≤20% because treatment was limited to lesions constituting ≤20% of T-BSA.Ruxolitinib creamResponders, n/N (%)1.5% once daily1.5% twice dailyT-VASI50†Percentage change from baseline differs for each body region, and the value for all body regions is based on the sum of all regions; binary outcomes (ie, yes/no) for T-VASI50 may not follow the distribution of percentage change from baseline.7/19 (36.8)9/20 (45.0) Head/neck6/19 (31.6)12/20 (60.0) Trunk7/18 (38.9)5/17 (29.4) Upper extremities7/18 (38.9)9/17 (52.9) Lower extremities6/18 (33.3)10/19 (52.6) Hands4/19 (21.1)3/20 (15.0) Feet5/19 (26.3)5/17 (29.4)T-VASI75†Percentage change from baseline differs for each body region, and the value for all body regions is based on the sum of all regions; binary outcomes (ie, yes/no) for T-VASI50 may not follow the distribution of percentage change from baseline.2/19 (10.5)3/20 (15.0) Head/neck5/19 (26.3)11/20 (55.0) Trunk4/18 (22.2)2/17 (11.8) Upper extremities3/18 (16.7)4/17 (23.5) Lower extremities3/18 (16.7)5/19 (26.3) Hands4/19 (21.1)1/20 (5.0) Feet4/19 (21.1)3/17 (17.6)T-BSA, Total body surface area; T-VASI50, ≥50% improvement from baseline in total Vitiligo Area Scoring Index; T-VASI75, ≥75% improvement from baseline in total Vitiligo Area Scoring Index.∗ T-VASI50 and T-VASI75 responses are reported for the subset of patients with baseline T-BSA ≤20% because treatment was limited to lesions constituting ≤20% of T-BSA.† Percentage change from baseline differs for each body region, and the value for all body regions is based on the sum of all regions; binary outcomes (ie, yes/no) for T-VASI50 may not follow the distribution of percentage change from baseline. Open table in a new tab T-BSA, Total body surface area; T-VASI50, ≥50% improvement from baseline in total Vitiligo Area Scoring Index; T-VASI75, ≥75% improvement from baseline in total Vitiligo Area Scoring Index. In summary, ruxolitinib cream demonstrated trends for clinical activity for treating vitiligo across demographics and clinical characteristics, including in patients with longstanding and extensive disease. F-VASI50 responses were observed in >40% of patients previously treated with topical corticosteroids or topical calcineurin inhibitors and in two-thirds of patients who received prior phototherapy. Ruxolitinib cream also produced a clinically meaningful repigmentation of all body areas, including acral areas, which are notoriously difficult to repigment.4Esmat S.M. El-Tawdy A.M. Hafez G.A. et al.Acral lesions of vitiligo: why are they resistant to photochemotherapy?.J Eur Acad Dermatol Venereol. 2012; 26: 1097-1104Crossref PubMed Scopus (34) Google Scholar Overall, these findings support the use of ruxolitinib cream for treating vitiligo. Reported analyses were descriptive, and sample sizes were small, warranting confirmation of results in larger populations. Dr Hamzavi has served as an advisory board member for AbbVie; a consultant for Incyte Corporation, Pfizer, and UCB; a principal investigator for AbbVie, Allergan, Bayer, Clinuvel Pharmaceuticals, Estée Lauder, Ferndale Laboratories, Galderma Laboratories LP, GE Healthcare, Incyte Corporation, Janssen, Janssen Biotech, Johnson & Johnson, Lenicura, LEO Pharma, Pfizer, and Unigen; a subinvestigator for Amgen, Bristol Myers Squibb, Foamix Pharmaceuticals, and Janssen; president of the HS Foundation; and cochair of the Global Vitiligo Foundation. Dr Rosmarin has received honoraria as a consultant for AbbVie, Celgene, Dermavant Sciences, Dermira, Eli Lilly and Company, Janssen, Kyowa Kirin, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio; research support from AbbVie , Amgen , Bristol Myers Squibb , Celgene , Dermira , Eli Lilly and Company , Incyte Corporation , Janssen , Merck , Novartis , Pfizer , and Regeneron Pharmaceuticals ; and has served as a paid speaker for AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi. Dr Harris 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/GSK, Sun Pharmaceuticals, TeVido BioDevices, and Villaris Therapeutics; holds equity in Rheos Medicines, TeVido BioDevices, and Villaris Therapeutics; is a scientific founder of Villaris Therapeutics; and has patents pending for IL-15 blockade for treating vitiligo, JAK inhibition with light therapy for vitiligo, and CXCR3 antibody depletion for the treatment of vitiligo. Dr Pandya has served as an investigator for Aclaris Therapeutics, Immune Tolerance Network, Incyte Corporation, and Pfizer; a consultant for Arcutis, Avita Medical, Chromaderm, Immune Tolerance Network, Incyte Corporation, Pfizer, Viela Bio, and Villaris; and a board member who also holds stock options for Clarify Medical and Tara Medical. Dr Lebwohl is an employee of Mount Sinai Hospital, which receives research funds from AbbVie , Amgen , Arcutis , Avotres , Boehringer Ingelheim , Dermavant , Eli Lilly , Incyte Corporation , Janssen Research & Development , LLC, Ortho Dermatologics , Regeneron , and UCB , Inc; 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. Dr Gottlieb has received honoraria as an advisory board member and consultant for AnaptysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Incyte Corporation, Janssen, LEO Pharma, Novartis, Sun Pharmaceuticals, and UCB; has stock options in Xbiotech; and has received institutional research/educational grants from Boehringer Ingelheim , Incyte Corporation , Janssen , Novartis , UCB , Xbiotech , and Sun Pharmaceuticals to Mount Sinai School of Medicine. Drs Butler, Kuo, and Sun are employees and shareholders of Incyte Corporation. Dr Grimes has served as a consultant for Aclaris Therapeutics, Clarify Medical, DermaForce, Incyte Corporation, Proctor & Gamble, and Versicolor Technologies and a principal investigator for Aclaris Therapeutics, Allergan/SkinMedica, Clinuvel Pharmaceuticals, Incyte Corporation, Johnson & Johnson, L'Oreal, Merz Pharma, Pfizer, Thync Global Inc, and VT Cosmetics. The study was funded by Incyte Corporation (Wilmington, DE). Writing assistance was provided by Laurie Orloski, PharmD, of ICON (North Wales, PA) and was funded by Incyte Corporation.