Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

Autor: King B; Department of Dermatology, Yale School of Medicine, New Haven, Connecticut. Electronic address: brett.king@yale.edu., Senna MM; Department of Dermatology, Lahey Hair Loss Center of Excellence, Lahey Hospital and Medical Center, Burlington, Massachusetts., Mesinkovska NA; Department of Dermatology, University of California, Irvine, California., Lynde C; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Lynderm Research Inc., Probity Medical Research, Markham, Ontario, Canada., Zirwas M; DOCS Dermatology, Columbus, Ohio., Maari C; Faculty of Medicine, Department of Medicine, University of Montreal, Montreal, Quebec, Canada., Prajapati VH; Division of Dermatology, Department of Medicine, and Sections of Community Pediatrics and Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada; Dermatology Research Institute, Probity Medical Research, Skin Health & Wellness Centre, Calgary, Alberta, Canada., Sapra S; Institute of Cosmetic and Laser Surgery, Oakville, Ontario, Canada., Brzewski P; Department of Dermatology, Jagiellonian University, Krakow, Poland., Osman L; Quest Dermatology Research, Northridge, California., Hanna S; Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Ontario, Canada; Dermatology On Bloor, Toronto, Ontario, Canada., Wiseman MC; Section of Dermatology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada., Hamilton C; Sun Pharmaceutical Industries, Inc., Lexington, Massachusetts., Cassella J; Sun Pharmaceutical Industries, Inc., Lexington, Massachusetts.
Jazyk: angličtina
Zdroj: Journal of the American Academy of Dermatology [J Am Acad Dermatol] 2024 Nov; Vol. 91 (5), pp. 880-888. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1016/j.jaad.2024.06.097
Abstrakt: Background: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA.
Objective: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated the safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA.
Methods: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo for 24 weeks. The primary end point was the percentage of patients achieving a Severity of Alopecia Tool score ≤20. A key secondary end point was the percentage of satisfaction of hair patient-reported outcome responders.
Results: Significantly higher proportions of patients taking deuruxolitinib met the primary end point (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary end points versus placebo, including satisfaction of hair patient-reported outcome (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors.
Limitations: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation.
Conclusion: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.
Competing Interests: Conflicts of interest Dr King has served on advisory boards and/or is a consultant and/or is a clinical trial investigator for AbbVie, AltruBio Inc, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol Myers Squibb, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Equillium, Horizon Therapeutics, Eli Lilly, Incyte Corp., Janssen Pharmaceuticals, LEO Pharma, Otsuka/Visterra Inc, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharmaceutical Industries Limited, TWi Biotechnology Inc, and Viela Bio Inc; also served on speaker bureaus for AbbVie, Incyte, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme and is a scientific advisor for BiologicsMD. Dr Senna has been a speaker for Eli Lilly and Pfizer and a principal investigator and/or received research funding from Follica, Eli Lilly, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Santiste Medical, and LEO Pharma; has also served on scientific advisory boards and/or been a consultant for Eli Lilly, Follica, L'Oreal, Kintor, and Pfizer, and is on the board of directors/medical advisory board for the National Alopecia Areata Foundation, Scarring Alopecia Foundation, and the American Hair Research Society. Dr Mesinkovska has been an advisor for CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Eli Lilly, and Pfizer, a principal investigator for AbbVie, Arcutis Biotherapeutics, Bristol Myers Squibb, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Eli Lilly, and Pfizer and a speaker for Eli Lilly. Dr Lynde has been a speaker and/or consultant for AbbVie, Amgen, Aralez, Arcutis, Bausch Health, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Dermavant, Devonian, Eli Lilly, Fresenius Kabi, Galderma, GSK, Incyte, Innovaderm, Intega Skin, Janssen, Kyowa Kirin, La Roche Posay, LEO Pharma, L'Oreal, Medexus, MedX, Merck, Novartis, P&G, Pediapharm, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sandoz, Sentrex, Sun Pharmaceutical Industries Limited, TEVA, Tribute, UCB, Viatris, and Volo Health; and has also been a principal investigator for AbbVie, Acelyrin, Akros, Altius, Amgen, Aralez, Arcutis, Avillion, Bausch Health, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cipher, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Dermavant, Devonian, Eli Lilly, Evelo, Galderma, GSK, Incyte, Innovaderm, Intega Skin, Janssen, Kyowa Kirin, La Roche Posay, LEO Pharma, L'Oreal, Medexus, MedX, Merck, MoonLake, Novartis, P&G, Pediapharm, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sandoz, Sentrex, Sun Pharmaceutical Industries Limited, TEVA, Tribute, UCB, Valeant, Viatris, and Volo Health. Dr Zirwas has been an investigator and/or speaker and/or consultant for AbbVie, Acrotech, Aldeyra, Advanced Derm Solutions, All Free Clear/Sun, Amgen, Anaptys Bio, Apogee, Arcutis, Bausch and Lomb, Biocon, Bristol Myers Squibb, Cara, Castle Biosciences, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Connect Biopharma, Dermavant, Edessa Biotech, EPI Health, Evelo, Galderma, Genentech/Novartis, Incyte, Janssen, L'Oreal, LEO Pharma, Level-Ex, Eli Lilly, LUUM, Nimbus, Oculus, Peloton, Pfizer, Regeneron/Sanofi, Trevi, Trifecta, and UCB; has also been an advisor for Vial and is part owner of AsepticMD. Dr Maari has served on advisory boards and/or is a consultant and/or is a clinical trial investigator for AbbVie, Almirall, AnaptysBio, Arena Pharmaceuticals, Bristol Myers Squibb, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Horizon Therapeutics, Eli Lilly, Incyte Corp., Janssen Pharmaceuticals, LEO Pharma, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharmaceutical Industries Limited, Valeant, Dermavant, Novartis, Amgen, and UCB. Dr Prajapati has been an advisor, consultant, and/or speaker for AbbVie, Actelion, Amgen, Aralez, Arcutis, Aspen, Bausch Health, BioScript Solutions, Boehringer Ingelheim, Bristol Myers Squibb, Canadian Psoriasis Network, Celgene, Cipher, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), CorEvitas, Eczema Society of Canada, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, Janssen, LEO Pharma, Medexus, Novartis, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharmaceutical Industries Limited, Tribute, UCB, and Valeant; investigator for AbbVie, AnaptysBio, Arcutis, Arena, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Nimbus Lakshmi, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Sanofi Genzyme, Takeda, and UCB; received grants from AbbVie, Bausch Health, Janssen, LEO Pharma, Novartis, and Sanofi Genzyme. Dr Sapra has been a principal investigator, consultant, or speaker for AbbVie, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Dermavant, Eli Lilly, Galderma, GSK, Incyte, Innovaderm, Janssen, LEO Pharma, Merz, Novartis, Pfizer, Pulse Biosciences, Regeneron, Roche, Sanofi, UCB, and Valeant. Dr Brzewski has been a principal investigator and/or consultant for AbbVie, Acelyrin, Alvotech Swiss, Amgen, BenevolentAI, Bioeq GmbH, Biogen, Celltrion, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Eli Lilly, Horizon Therapeutics, Janssen, LEO Pharma, Pfizer, Regeneron, and Samsung Bioepis. Dr Osman has been an advisor for AbbVie, Affibody, Allergan, Amgen, AnaptysBio, Arcutis, Aurigene, Botanix, Castle Biosciences, Chemocentryx, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Dermavant, DS Biopharma, Eli Lilly, Foamix Pharmaceuticals, Galderma, Janssen, Incyte, LEO Pharma, Reistone, Sun Pharmaceutical Industries Limited, and Valeant. Dr Hanna has been an advisory board member, principal investigator, investigator, speaker, and/or consultant for AbbVie, Akros, Allergan, Altius Healthcare, Amgen, Aralez, Arcutis, Bausch Health, Biopharma, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Cutanea, Dermira, Galapagos, Galderma, Glenmark, Incyte, Janssen, LEO Pharma, Lilly, Lumenis, Merz, Novartis, Pediapharma, Pfizer, Prollenium, Regeneron, Revanesse, Reistone, Sandoz, Sanofi, Sun Pharma, and UCB. Dr Wiseman has been a principal investigator, consultant, advisor, or speaker for Acelyrin, AbbVie (previously Abbott), Akros, Amgen, Arcutis, Asana BioSciences, AstraZeneca, Bausch Health, Bristol Myers Squibb, CoNCERT Pharmaceuticals (subsequently acquired by Sun Pharmaceutical Industries Limited), Celgene, Dermavant, Dermira, Dice, Eli Lilly, Evelo, Galderma, Glenmark, Incyte, Janssen, LEO Pharma A/S, L'Oreal, Merck Frosst Canada, Moonlake, Novartis, Pfizer, Principia, PRCL Research, Regeneron, Sanofi, Takeda, Timber. Drs Hamilton and Cassella are employees of Sun Pharmaceutical Industries, Inc.
(Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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