Adults with dermatomyositis that were resistant to previous therapy who received brepocitinib 30 mg daily had higher Total Improvement Scores at 52 weeks than those who received placebo in a phase 3 randomized trial published in The New England Journal of Medicine.
The VALOR trial was a multicenter, double-blind, randomized, placebo-controlled trial conducted at 90 sites in 20 countries. Researchers randomly assigned 241 adults with active muscle and skin disease in a 1:1:1 ratio to receive once-daily oral brepocitinib 30 mg, brepocitinib 15 mg, or placebo for 52 weeks while continuing standard therapies.
The Total Improvement Score, a composite myositis index ranging from 0 to 100, with higher scores indicating greater improvement, was the primary end point. At week 52, the mean Total Improvement Score was 47 in the brepocitinib 30-mg group, 38 in the brepocitinib 15-mg group, and 31 in the placebo group. The brepocitinib 30-mg group showed a statistically significant difference vs placebo, whereas the 15-mg group did not.
Eligible patients were aged 18 to 75 years and had evidence of active muscle disease and active skin disease, along with an inadequate response to at least one traditional therapy, including systemic glucocorticoids, conventional disease-modifying antirheumatic drugs, or intravenous immune globulin.
At baseline, 81% of patients had moderate-to-severe disease activity, 76% were receiving systemic glucocorticoids, and 81% were receiving at least 2 dermatomyositis-directed systemic therapies. Previous treatment with intravenous immune globulin was reported in 25% of patients, rituximab in 11%, and cyclophosphamide in 7%.
Researchers reported that brepocitinib 30 mg was superior to placebo across all 9 prespecified multiplicity-controlled secondary end points. Moderate improvement, defined as a Total Improvement Score of at least 40, occurred in 68% of patients receiving brepocitinib 30 mg vs 44% receiving placebo. Major improvement, defined as a Total Improvement Score of at least 60 among eligible patients, occurred in 46% vs 26%, respectively.
Among patients receiving systemic glucocorticoids at baseline, 62% in the brepocitinib 30-mg group tapered to 2.5 mg or less of prednisone equivalent daily between weeks 48 and 52 compared with 34% in the placebo group. Complete tapering to 0 mg daily occurred in 42% vs 23%, respectively. Moderate improvement at week 52 with minimal-to-no systemic glucocorticoid use at both weeks 48 and 52 occurred in 54% of patients receiving brepocitinib 30 mg vs 27% receiving placebo.
Improvements in cutaneous disease activity were observed by week 4 and continued through week 52. The mean change from baseline in Cutaneous Dermatomyositis Disease Area and Severity Index–Activity score at week 52 was −12 with brepocitinib 30 mg vs −7 with placebo.
In an exploratory analysis of patients with moderate-to-severe skin disease at baseline, cutaneous clinical remission at week 52 occurred in 44% of patients receiving brepocitinib 30 mg compared with 21% receiving placebo.
The mean change from baseline in Health Assessment Questionnaire–Disability Index score at week 52 was −0.34 in the brepocitinib 30-mg group vs −0.04 in the placebo group. Median time to sustained moderate improvement was 85 days with brepocitinib 30 mg compared with 168 days with placebo.
Safety analyses showed adverse events in 90% of patients receiving brepocitinib 30 mg, 86% receiving brepocitinib 15 mg, and 91% receiving placebo. Serious infections occurred more frequently with brepocitinib 30 mg, occurring in 10% of patients compared with 1% in the placebo group. During the trial period no mortality events or opportunistic infections were reported.
The researchers noted limitations including that background disease-modifying antirheumatic drug therapy was required to remain stable throughout the blinded treatment period, including among patients with marked clinical improvement. They wrote that data from the ongoing open-label extension may help characterize brepocitinib use under more flexible background-therapy conditions.
“In this trial, we found that daily brepocitinib administered at a dose of 30 mg (but not at a dose of 15 mg) was superior to placebo in the treatment of dermatomyositis in a representative patient population receiving standard therapies,” wrote lead study author Ruth Ann Vleugels, MD, MPH, of Mass General Brigham Department of Dermatology, Harvard Medical School, and colleagues.
Disclosures: The trial was funded by Priovant Therapeutics. Full disclosures can be found in the published study.
