ARTICLE: A Phase 3 Trial of Brepocitinib in Dermatomyositis
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, Griger Zoltan, 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 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 Jr, Jiri Vencovsky, Anthony P Fernandez, David Fiorentino, Lisa Christopher-Stine, Victoria P Werth, Rohit Aggarwal 43; VALOR Investigators
*co-first authors
JOURNAL: N Engl J Med. 2026 Mar 28. doi: 10.1056/NEJMoa2503531. Online ahead of print.
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.).
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