Once-daily brepocitinib 30 mg may improve skin disease activity, itching, and skin-related quality of life compared with placebo in patients with dermatomyositis.
Investigators used data from the 52-week, double-blind, placebo-controlled VALOR trial, conducted at 90 sites across 20 countries between October 2022 and July 2025. They enrolled 241 patients aged 18 to 75 years with active skin and muscle disease. Participants were randomly assigned to receive once-daily oral brepocitinib 30 mg (n = 81), brepocitinib 15 mg (n = 81), or placebo (n = 79). The analysis focused on the 30-mg dose because the 15-mg dose did not demonstrate superiority over placebo on the parent trial's primary efficacy endpoint.
Key secondary outcomes included changes in the Cutaneous Dermatomyositis Disease Area and Severity Index–Activity (CDASI-A) score at weeks 4 and 52 and achievement of clinically meaningful skin improvement at week 52, defined as a reduction of at least 40% and 4 points from baseline. Exploratory outcomes included itch severity, skin-related quality of life, achievement of clear or almost clear skin with at least a 2-point improvement on the Investigator's Global Assessment (IGA), and functional skin remission, defined as a CDASI-A score of 5 or lower.
At week 52, 50 patients (62%) receiving brepocitinib 30 mg achieved clinically meaningful skin improvement vs. 35 patients (44%) receiving placebo, an adjusted difference of 16.8 percentage points. At week 4, 27 patients (33%) receiving brepocitinib met the response threshold vs. 14 patients (18%) receiving placebo. Greater reductions in skin disease activity with brepocitinib were sustained throughout the treatment period.
Remission-oriented outcomes favored brepocitinib. Among patients with moderate to severe skin disease at baseline, 21 patients (46%) receiving brepocitinib achieved clear or almost clear skin with at least a 2-point improvement on the IGA at week 52 vs. 12 patients (22%) receiving placebo. Functional skin remission was achieved by 20 patients (44%) receiving brepocitinib vs. 11 patients (21%) receiving placebo.
By week 4, itch remission was achieved by 31 patients (38%) receiving brepocitinib vs. 15 patients (19%) receiving placebo. Among patients with at least moderate itching at baseline, 27 patients (54%) receiving brepocitinib experienced a reduction of at least 2 points in itch severity at week 4 vs. 4 patients (10%) receiving placebo. Corresponding proportions were 74% and 33% at week 52.
Skin-related quality of life improved early and remained better throughout treatment. At week 4, the mean reduction in Skindex-16 score was 12.9 points with brepocitinib vs. 0.9 points with placebo. The improvement with brepocitinib exceeded the 10-point threshold considered clinically meaningful, with sustained benefits observed through week 52.
Brepocitinib was associated with greater reductions in oral corticosteroid use. Among patients receiving corticosteroids at baseline, 37 patients (62%) in the brepocitinib group reduced their prednisone-equivalent dose to 2.5 mg/d or less by weeks 48 to 52 vs. 22 patients (34%) receiving placebo. Complete corticosteroid discontinuation was achieved by 25 patients (42%) receiving brepocitinib vs. 15 patients (23%) receiving placebo.
Overall adverse-event rates were similar between groups, occurring in 73 patients (90%) receiving brepocitinib 30 mg and 72 patients (91%) receiving placebo. However, serious infections occurred more frequently with brepocitinib, affecting 8 patients (10%) vs. 1 patient (1%), respectively. Most serious infections were respiratory and were managed with standard medical care. No mortality was reported.
The investigators identified the requirement for stable background treatment with conventional disease-modifying antirheumatic drugs throughout the blinded treatment period as a limitation, because these medications are commonly tapered following clinical improvement in routine practice. Several skin-specific outcomes were exploratory and were not adjusted for multiple comparisons. The 52-week treatment period also left longer-term efficacy and safety to be evaluated.
“These findings suggest that more ambitious treatment goals are attainable, even in patients with high baseline disease activity,” wrote lead study author Aaron R. Mangold, MD, of the Department of Dermatology at Mayo Clinic, and colleagues.
Full disclosures of the study authors can be found in the study.
Source: JAMA Dermatology
