A Phase 3 Trial of Brepocitinib in Dermatomyositis

Authors

• Ruth Ann Vleugels, Mass General Brigham Department of Dermatology, Harvard Medical School, Boston.
• Julie J. Paik, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
• Iazsmin Bauer Ventura, Division of Rheumatology, Department of Medicine, University of Chicago, Chicago.
• Aaron R. Mangold, Department of Dermatology, Mayo Clinic, Scottsdale, AZ.
• Prateek C. Gandiga, Division of Rheumatology, Department of Medicine, Emory University, Atlanta.
• Anna Haemel, Department of Dermatology, University of California, San Francisco, San Francisco.
• Hector Chinoy, Department of Rheumatology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, United Kingdom.
• Yessar M. Hussain, Department of Neurology, University of Texas Dell Medical School, Austin.
• Kumaraswamy Sivakumar, Neuromuscular Research Center, Phoenix, AZ.
• Griger Zoltan, Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.
• Eun Bong Lee, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
• Francisca Bozan, Section of Rheumatology, Department of Medicine, Hospital Clinico Universidad de Chile, Santiago.
• Chung-Yuan Hsu, Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
• Alisa Femia, Ronald O. Perelman Department of Dermatology, New York University, New York.
• Mazen M. Dimachkie, Neuromuscular Division, Department of Neurology, University of Kansas Medical Center, Kansas City.
• Michelle S. Min, Department of Dermatology, University of California Irvine School of Medicine, Irvine.
• Tahseen Mozaffar, Department of Neurology, University of California Irvine School of Medicine, Irvine.
• Christina Charles-Schoeman, Division of Rheumatology, University of California, Los Angeles, Los Angeles.
• David R. Fernandez, Division of Rheumatology, Hospital of Special Surgery and Weill Cornell Medicine, New York.
• Oluwakemi Onajin, Section of Dermatology, Department of Medicine, University of Chicago, Chicago.
• Raquel Marques, Department of Rheumatology, Unidade Local de Saude Santa Maria, Centro Academico de Medicina de Lisboa, Lisbon, Portugal.
• Galina Marder, Division of Rheumatology, Department of Medicine, Zucker School of Medicine at Northwell Health, Great Neck, NY.
• Floranne Ernste, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
• Elena Schiopu, Division of Rheumatology, Medical College of Georgia at Augusta University, Augusta.
• Jason Sluzevich, Department of Dermatology, Mayo Clinic, Jacksonville, FL.
• David Pearson, Department of Dermatology, University of Minnesota, Minneapolis.
• Stephen Lindsey, LSU Health Sciences Center - New OrleansFollow
• Michael Luggen, Division of Rheumatology, Allergy, and Immunology, University of Cincinnati College of Medicine, Cincinnati.
• Michael R. Bubb, University of Florida College of Medicine, Gainesville.
• et al.

Document Type

Article

Publication Date

3-28-2026

Publication Title

The New England journal of medicine

Abstract

BACKGROUND: Brepocitinib is a first-in-class, oral, selective TYK2-JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence. RESULTS: A total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P< 0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, -2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial. CONCLUSIONS: In adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.).

PubMed ID

41910335

Publisher

Massachusetts Medical Society

Comments

Featured in Faculty Publications Display; May 2026

Rights

Copyright © 2026 Massachusetts Medical Society.

Recommended Citation

Vleugels, Ruth Ann; Paik, Julie J.; Bauer Ventura, Iazsmin; Mangold, Aaron R.; Gandiga, Prateek C.; Haemel, Anna; Chinoy, Hector; Hussain, Yessar M.; Sivakumar, Kumaraswamy; Zoltan, Griger; Lee, Eun Bong; Bozan, Francisca; Hsu, Chung-Yuan; Femia, Alisa; Dimachkie, Mazen M.; Min, Michelle S.; Mozaffar, Tahseen; Charles-Schoeman, Christina; Fernandez, David R.; Onajin, Oluwakemi; Marques, Raquel; Marder, Galina; Ernste, Floranne; Schiopu, Elena; Sluzevich, Jason; Pearson, David; Lindsey, Stephen; Luggen, Michael; Bubb, Michael R.; and al., et, "A Phase 3 Trial of Brepocitinib in Dermatomyositis" (2026). School of Medicine Faculty Publications. 4644.
https://digitalscholar.lsuhsc.edu/som_facpubs/4644
10.1056/NEJMoa2503531