A Phase 3 Trial of Brepocitinib in Dermatomyositis

Clinical Snapshot

Key Findings

• P Value: P<0.001

• Effect Size: 15.3-point improvement with brepocitinib 30mg vs placebo

• Primary Outcome: Total Improvement Score at week 52: 46.5 (30mg), 37.5 (15mg), 31.2 (placebo)

• Nnt Or Sensitivity: NNT not calculable from provided data; effect size represents 15% improvement on 100-point scale

• Confidence Interval: 95% CI: 6.7 to 24.0

Clinical Application

Oral administration enhances feasibility, but requires careful infection monitoring and specialist oversight Would require TGA approval and PBS listing. Likely restricted to specialist rheumatology/dermatology centres given safety profile and cost considerations Adults with treatment-resistant dermatomyositis requiring systemic therapy beyond conventional immunosuppressants

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.).

References

1. 1.Vleugels, R. A., Paik, J. J., Bauer Ventura, I., Mangold, A. R., Gandiga, P. C., Haemel, A., Chinoy, H., Hussain, Y. M., Sivakumar, K., Griger, Z., Lee, E. B., Bozan, F., Hsu, C. Y., Femia, A., Dimachkie, M. M., Min, M. S., Mozaffar, T., Charles-Schoeman, C., Fernandez, D. R., ... Aggarwal, R. (2026). A Phase 3 Trial of Brepocitinib in Dermatomyositis. *New England Journal of Medicine*. https://doi.org/10.1056/NEJMoa2503531