Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.

Background: Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata.
Methods: In this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807.
Findings: Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p<0·0001), 20·8% (13·7-29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7-30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7-20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths.
Interpretation: Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy.
Funding: Pfizer.
Competing Interests: Declaration of interests BK served on advisory boards or was a consultant or clinical trial investigator for AbbVie, AltruBio, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Therapeutics, BMS, Concert Pharmaceuticals, Equillium, Horizon Therapeutics, Eli Lilly, Incyte, Janssen Pharmaceuticals, LEO Pharma, Otsuka/Visterra, Pfizer, Regeneron, Sanofi Genzyme, TWi Biotechnology, and Viela Bio. BK is on speaker bureaus for AbbVie, Incyte, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme. WGH was a scientific advisor or clinical study investigator for Beiersdorf/Eucerin, BioNOOX, Eucerin, Galderma, GSK, Janssen, Johnson & Johnson, Pfizer, and Sanofi. JCS was scientific advisor or consultant for AbbVie, LEO Pharma, Novartis, Sandoz, Sanofi Genzyme, Trevi, and Viofor; speaker for AbbVie, Eli Lilly, Janssen-Cilag, LEO Pharma, and Sanofi Genzyme; and investigator for AbbVie, Amgen, BMS, Galderma, Galapagos, Incyte, InfraRx, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB. JS was a consultant or clinical study investigator for 30 Madison, Eirion, Eli Lilly, Pfizer, and Regenlab; and stockholder of 30 Madison. CL was speaker or consultant for AbbVie, Altius, Amgen, Aralez, Arcutis, Bausch Health, Bayer, Boehringer Ingelheim, BMS, Celgene, Cipher, Dermavant, Eli Lilly, Fresenius Kabi, GSK, Innovaderm, Intega Skin, Janssen, Kyowa, La Roche Posay, LEO Pharma, L'Oreal, Medexus, Merck, P&G, Pediapharm, Regeneron, Roche, Sanofi Genzyme, Sentrex, TEVA, Tribute, UCB, Valeant, and Viatris; and principal investigator for AbbVie, Amgen, Aralez, Arcutis, Bausch Health, Bayer, Boehringer Ingelheim, BMS, Celgene, Cipher, Dermavant, Eli Lilly, GSK, Innovaderm, Janssen, Kyowa, LEO Pharma, L'Oreal, Merck, Pediapharm, Regeneron, Roche, Sanofi Genzyme, Tribute, UCB, and Valeant. NAM provided professional services for AbbVie, Arena Pharmaceuticals, BMS, Concert Pharmaceuticals, Eli Lilly, La Roche Posay, and Pfizer. RS provided professional services to Aerotech, AbbVie, AstraZeneca, Akesobio, Amgen, Arcutis, Arena, Ascend, Bayer, BMS, Boehringer Ingelheim, Celgene, Coherus BioSciences, Connect, Cutanea, Dermira, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, MedImmune, Merck, MSD, Novartis, Oncobiologics, Pfizer, Regeneron, Reistone, Roche, Samson Clinical, Sanofi, Sun Pharma, and UCB. SHZ, LN, DW, AF, DM, VP, and RW are employees of and own stock in Pfizer. RF was an employee of and owned stock in Pfizer at the time of this study. XZ declares no competing interests.
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