Efficacy and safety of the oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase IIb/III and long-term phase III clinical studies in alopecia areata
- PMID: 39432738
- DOI: 10.1093/bjd/ljae365
Efficacy and safety of the oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase IIb/III and long-term phase III clinical studies in alopecia areata
Abstract
Background: The ALLEGRO phase IIa and IIb/III (NCT02974868 and NCT03732807) studies have demonstrated that ritlecitinib is effective and well tolerated in adults and adolescents with alopecia areata (AA) up to 48 weeks.
Objectives: To assess the efficacy of ritlecitinib through month 24 and safety through data cutoff in the ALLEGRO phase IIb/III study and the ongoing long-term open-label phase III ALLEGRO-LT study (NCT04006457).
Methods: Patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss from ALLEGRO IIb/III who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) scores of ≤ 20 and ≤ 10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth were reported through month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data [last observation carried forward (LOCF)] were reported up to 9 December 2022. Safety was assessed throughout.
Results: At month 12, a SALT score ≤ 20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200 mg/50 mg, respectively. At month 24, these proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at month 24 [EBA observed: 57.6% (50 mg), 61.0% (200/50 mg); EBA LOCF: 46.8% (50 mg), 50.9% (200/50 mg); ELA observed: 51.2% (50 mg), 62.7% (200/50 mg); ELA LOCF: 43.2% (50 mg), 51.7% (200/50 mg)]. PGI-C response was achieved by patients at month 24 [observed: 70.0% (50 mg), 76.4% (200/50 mg); LOCF: 56.6% (50 mg), 65.5% (200/50 mg)]. Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib.
Conclusions: Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥ 12 years with AA.
Plain language summary
Alopecia areata is a condition where the immune system mistakenly attacks hair follicles, causing hair loss. It affects around 2% of people worldwide, including children and adults. Alopecia areata may involve small patches or complete hair loss on the scalp and/or body. People with alopecia areata may need to use medicines for a long time to manage hair loss. There are not many treatment options available. Ritlecitinib is a pill taken daily to treat severe alopecia areata. It blocks the steps that cause hair loss. In this study, we looked at how well ritlecitinib worked over 2 years in people aged 12 years and older with alopecia areata who had lost at least half of their scalp hair. We measured hair loss on the scalp, eyebrows and eyelashes, as well as how satisfied people were with their hair regrowth. We also looked at how safe ritlecitinib was when taken for 2 years. A total of 191 people from 17 countries took the approved dose of ritlecitinib. After 1 year, 74 of 164 people (45%) had scalp hair regrowth (20% or less scalp hair loss), increasing to 61% after 2 years. For every 8 out of 10 people, their scalp hair regrowth was maintained from 1 to 2 years. Eyebrow and eyelash hair regrowth also increased over 2 years. Around 8 out of 10 people were satisfied with their hair growth after 2 years, and the safety of ritlecitinib was as expected from the studies done before. The results show that ritlecitinib is effective and appropriate for long-term use in people aged 12 years and older with alopecia areata.
© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.
Conflict of interest statement
Conflicts of interest: M.P. has been a consultant and/or investigator for Pfizer, Eli Lilly and Procter & Gamble. J. Soung has been a speaker for Celgene, Regeneron/Sanofi and Ortho Dermatologics; a speaker and investigator for Amgen, AbbVie and Pfizer; a speaker, investigator and advisor for Eli Lilly; an investigator and advisor for LEO Pharma; an investigator, speaker and consultant for Novartis; an investigator for UCB, Janssen, Kyowa Kirin, KoBioLabs and Castel Biosciences; an investigator and consultant for Dermavant; a speaker and consultant for Bristol Myers Squibb; and a speaker, investigator and consultant for Arcutis. B.K. has been an advisory board member, consultant, clinical trial investigator and/or on data monitoring committees for AbbVie, AltruBio, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol Myers Squibb, Concert Pharmaceuticals, Equillium, Horizon Therapeutics, Eli Lilly, Incyte, Janssen Pharmaceuticals, LEO Pharma, Merck, Otsuka/Visterra, Pfizer, Q32 Bio, Regeneron, Sanofi Genzyme, Sun Pharmaceutical, TWi Biotechnology, Viela Bio and Ventyx Biosciences; and has served on speakers bureau for AbbVie, Incyte, Eli Lilly, Pfizer, Regeneron and Sanofi Genzyme. J. Shapiro has been a consultant for Pfizer and Eli Lilly, and a clinical trial investigator for Pfizer. L.R. has been a speaker for AbbVie, L’Oréal, LEO Pharma, Novartis, Pierre Fabre and Pfizer; and an advisory board member for LEO Pharma, Janssen, L’Oréal, Novartis, Pfizer, Sanofi and UCB. P.F. has been a consultant for Eli Lilly and an advisory board member and investigator for Pfizer. N.M. has received honoraria for participation in advisory boards, speaker and/or consultancy for AbbVie, Almirall, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dr. Wolff, Eli Lilly, Janssen, La Roche-Posay, LEO Pharma, Novartis, Pfizer and UCB Pharma. B.M.P. has received honoraria for participation in advisory boards, speaker and/or consultancy for Almirall, Pfizer, Eli Lilly, Pierre Fabre-Ducray, Cantabria-Difa Cooper, Dercos–L’Oréal, ISDIN and Legacy Healthcare. X.L., R.W., D.W., G.S. and A.L. are employees of, and hold stock or stock options in, Pfizer.
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