Skin-Specific Outcomes of Brepocitinib in Patients With Dermatomyositis: Secondary Analysis of a Phase 3 Randomized Clinical Trial

Authors

• Aaron R Mangold
• Anna Haemel
• Neda Shahriari
• Benjamin Chong
• Anthony P Fernandez
• David Fiorentino
• David Pearson
• Jason Sluzevich
• Oluwakemi Onajin
• Pranita V. Rambhatla, Henry Ford HealthFollow
• Mehdi Rashighi
• Charlotte Hurabielle
• David Fivenson
• Erin Boh
• Taraneh Paravar
• Ashley Crew
• R Hal Flowers
• Dustin Taylor
• Sweta Subhardashani
• Donna Culton
• Courtney Schadt
• Jeffrey Callen
• Christina Lam
• Lauren Graham
• Kimberly Hashemi
• Rochelle Castillo
• Andrea Maderal
• Scott Elman
• Katharina S Shaw
• Matthew D Cascino
• Avery LaChance
• Michelle S Min
• Alisa Femia
• Ruth Ann Vleugels
• Victoria P Werth

Recommended Citation

Mangold AR, Haemel A, Shahriari N, Chong B, Fernandez AP, Fiorentino D, Pearson D, Sluzevich J, Onajin O, Rambhatla PV, Rashighi M, Hurabielle C, Fivenson D, Boh E, Paravar T, Crew A, Flowers RH, Taylor D, Subhardashani S, Culton D, Schadt C, Callen J, Lam C, Graham L, Hashemi K, Castillo R, Maderal A, Elman S, Shaw KS, Cascino MD, LaChance A, Min MS, Femia A, Vleugels RA, Werth VP. Skin-Specific Outcomes of Brepocitinib in Patients with Dermatomyositis: Secondary Analysis of a Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2026.

Document Type

Article

Publication Date

8-26-2026

Publication Title

JAMA Dermatol

Abstract

IMPORTANCE: Brepocitinib, a first-in-class oral, selective TYK2 and JAK1 inhibitor, demonstrated broad efficacy in a phase 3 randomized clinical trial in dermatomyositis.

OBJECTIVE: To evaluate the effects of brepocitinib on cutaneous disease activity, itch, skin-related quality of life (QOL), and achievement of remission-level end points in adults with dermatomyositis over 52 weeks of treatment.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the 52-week, phase 3, double-blind, placebo-controlled, randomized VALOR clinical trial, conducted from October 2022 to July 2025 at 90 sites in 20 countries, included adults with dermatomyositis and active skin and muscle disease.

INTERVENTION: Once-daily brepocitinib, 30 mg; brepocitinib, 15 mg; or placebo.

MAIN OUTCOMES AND MEASURES: Key secondary outcomes in VALOR included change in the Cutaneous Dermatomyositis Disease Area and Severity Index-Activity (CDASI-A) score and achievement of clinically meaningful CDASI-A response (≥40% relative and ≥4-point absolute improvement). Exploratory outcomes included itch (Peak Pruritus Numeric Rating Scale [PP-NRS]); skin-related QOL (Skindex-16); achievement of Cutaneous Dermatomyositis Activity-Investigator's Global Assessment (CDA-IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point improvement; and functional skin remission (CDASI-A ≤5). Between-group differences were analyzed using ANCOVA or Cochran-Mantel-Haenszel methods.

RESULTS: The VALOR trial enrolled 241 participants (mean [SD] age, 50.6 [13.3] years; 187 [77.6%] female; 54 [22.4%] male). Beginning at week 4, brepocitinib, 30 mg, demonstrated superiority over placebo in mean (SD) change from baseline in CDASI-A score (-6.4 [5.8] vs -3.5 [6.0], respectively; difference, -3.0; 95% CI, -4.6 to -1.4; P <  .001) and resulted in greater achievement of clinically meaningful CDASI-A response (27 participants [33.3%] vs 14 participants [17.7%], respectively; difference, 15.1 percentage points [pp]; 95% CI, 1.7-28.6 pp), itch remission (PP-NRS ≤1: 31 participants [38.3%] vs 15 participants [19.0%], respectively; difference, 18.9 pp; 95% CI, 5.0-32.9 pp) and improvement in skin-related QOL (Skindex-16 score: -12.9 [21.6] vs -0.9 [22.4], respectively; difference, -11.9; 95% CI, -17.9 to -6.0). Benefits on these measures were observed at all time points from week 4 through week 52. Among the 155 participants (64.3%) with moderate to severe skin disease at baseline, brepocitinib, 30 mg, was also associated with higher rates of achievement of a CDA-IGA score of clear or almost clear compared with placebo (21 participants [45.7%] vs 12 participants [21.8%], respectively; difference, 21.1 pp at week 52; 95% CI, 2.5-39.7 pp) and functional skin remission (20 participants [43.5%] vs 11 participants [20.8%], respectively; difference at week 52, 26.6 pp; 95% CI, 7.6-45.5 pp). Brepocitinib exhibited a safety profile consistent with approved JAK and TYK2 inhibitors.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial in dermatomyositis, once-daily brepocitinib, 30 mg, resulted in rapid, durable, and remission-level control of skin disease with an acceptable safety profile.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05437263.

PubMed ID

42646746

ePublication

ePub ahead of print