TOPLINE

Oral brepocitinib, a first-in-class oral, selective tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) inhibitor, improved cutaneous disease activity, pruritus, and skin-related quality of life (QOL) through 52 weeks in adults with dermatomyositis in the prespecified secondary analysis of a phase 3 trial.

METHODOLOGY

• Researchers conducted a prespecified secondary analysis of the 52-week, phase 3, double-blind, placebo-controlled VALOR randomized clinical trial from October 2022 to July 2025 at 90 sites in 20 countries.
• A total of 241 adults (mean age, 50.6 years; 77.6% women; 67.9%-77.2% were White and 26.6%-28.4% were Hispanic) with dermatomyositis and active skin and muscle disease were randomized 1:1:1 to receive once-daily 30 mg brepocitinib, 15 mg brepocitinib, or placebo; this secondary analysis assessed 30-mg dose vs placebo data.
• Most participants (92.9%) received at least one systemic dermatomyositis treatment and 75.5% received systemic corticosteroids at baseline.
• Participants had active skin disease defined as Cutaneous Dermatomyositis Disease Area and Severity Index–Activity (CDASI-A) score ≥6 (scores range from 0 to 100, with higher scores indicating greater disease activity) and active muscle disease defined as Manual Muscle Testing 8 score of 80 to 142 (scores range from 0 to 150, with lower scores indicating weaker muscles).
• Key outcomes included CDASI-A activity and clinically meaningful CDASI-A response (≥40% relative and ≥4-point absolute improvement), itch assessed outcomes assessed by Peak Pruritus Numeric Rating Scale (PP-NRS); skin-related QOL measured by 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).

TAKEAWAY

• At week 52, 61.7% of patients in the 30-mg brepocitinib group achieved a clinically meaningful CDASI-A response vs 44.3% with placebo (difference, 16.8 percentage points; P = .04). At week 4, a higher proportion of patients in the 30 mg brepocitinib group achieved clinically meaningful CDASI-A response vs placebo (33.3% vs 17.7%, respectively; difference, 15.1 percentage points).
• Brepocitinib was associated with higher rates of itch remission (PP-NRS ≤1) at week 4 compared with placebo (38.3% vs 19.0%; difference, 18.9 percentage points) and improvement in skin-related QOL (Skindex-16 score: −12.9 vs −0.9; difference, −11.9; 95% CI, −17.9 to −6.0).
• Among the 155 participants (64.3%) with moderate to severe skin disease at baseline, brepocitinib, 30 mg, was associated with higher rates of achievement of clear or almost clear skin compared with placebo (45.7% vs 21.8%, respectively; difference, 21.1 percentage points) and functional skin remission (43.5% vs 20.8%, respectively; difference, 26.6 percentage points; 95% CI, 7.6-45.5 percentage points) at week 52.
• Among participants receiving oral corticosteroids at baseline, 61.7% treated with 30 mg brepocitinib were tapered to 2.5 mg daily dose or less by week 52, compared with 34.4% receiving placebo. Additionally, 41.7% of patients treated with brepocitinib successfully discontinued oral corticosteroids by week 52, compared with 23.4% in the placebo group. The rates of adverse events were similar between the two groups

IN PRACTICE

These results support 30 mg brepocitinib "as a targeted therapy capable of delivering rapid, remission-level control of skin disease in patients with dermatomyositis with a safety profile consistent with approved JAK and TYK2 inhibitors," the authors wrote. These findings, they added suggest  "more ambitious treatment goals are attainable, even in patients with high baseline disease activity."

SOURCE

The study was led by Aaron R. Mangold, MD, Department of Dermatology, Mayo Clinic, Scottsdale, Arizona. It was published online on August 26 in JAMA Dermatology.

LIMITATIONS

Disease-modifying antirheumatic drug therapy remained stable throughout the blinded treatment period.

DISCLOSURES

The study was supported by Priovant Therapeutics. Mangold and several authors reported receiving grants, personal fees, or research support from Priovant Therapeutics and other pharmaceutical companies, and some reported being employees or shareholders of Priovant. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.