A Phase 3 Trial of Brepocitinib in Dermatomyositis
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.).
Source: New England Journal of Medicine
Authors: Ruth Ann Vleugels, Julie J. Paik, Iazsmin Bauer Ventura, Aaron R. Mangold, Prateek C. Gandiga, Anna Haemel, Hector Chinoy, Yessar M. Hussain, Kumaraswamy Sivakumar, Zoltan Griger, Eun Bong Lee, Francisca Bozan, Chung-Yuan Hsu, Alisa Femia, Mazen M. Dimachkie, Michelle S. Min, Tahseen Mozaffar, Christina Charles-Schoeman, David R. Fernandez, Oluwakemi Onajin, Raquel Campanilho-Marques, Galina Marder, Floranne Ernste, Elena Schiopu, Jason Sluzevich, David Pearson, Stephen Lindsey, Michael Luggen, Michael R. Bubb, Erin Boh, Rashmi Maganti, Latisha Heinlen, Katharina S. Shaw, Matthew D. Cascino, Paul N. Mudd, Jiri Vencovsky, Anthony P. Fernandez, David Fiorentino, Lisa Christopher-Stine, Victoria P. Werth, Rohit Aggarwal
Institutions: Harvard University, Mass General Brigham, Johns Hopkins University, Johns Hopkins Medicine, University of Chicago, Mayo Clinic, Mayo Clinic in Arizona, Emory University, University of California, San Francisco, Manchester Academic Health Science Centre, University of Manchester, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, University of Debrecen, Seoul National University, Hospital Clínico de la Universidad de Chile, University of Chile, Kaohsiung Chang Gung Memorial Hospital, New York University, University of Kansas Medical Center, University of California, Irvine, University of California, Los Angeles, Hospital for Special Surgery, Weill Cornell Medicine, Centro Académico de Medicina de Lisboa, Unidade Local de Saúde Santa Maria, Northwell Health, Augusta University, Mayo Clinic in Florida, University of Minnesota, Louisiana State University, Louisiana State University Health Sciences Center New Orleans, University of Cincinnati, University of Florida Health, University of Florida, Tulane University, Baylor College of Medicine, Children's Hospital of Philadelphia, Institute of Rheumatology, Cleveland Clinic, Stanford Medicine, Stanford University, Philadelphia VA Medical Center, University of Pennsylvania, University of Pittsburgh
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7142357879