DENVER — A first-in-class oral, selective TYK2-JAK1 inhibitor showed clinical benefit in adults with dermatomyositis who had not responded to prior therapies, in a phase 3, double-blind, randomized, placebo-controlled trial. 

At week 52, 81 patients aged 18-75 treated with brepocitinib 30 mg daily reached a mean Total Improvement Score, the primary endpoint, of 46.5 vs 37.5 in 81 patients taking a 15-mg daily dose and 31.2 in 79 patients in the placebo group (difference vs placebo, 15.3 for the 30-mg dose, P < .001; 6.3 for the 15-mg dose, which was not statistically significant). The results were reported by Ruth Ann Vleugels, MD, MPH, chair of dermatology at Brigham and Women’s Hospital and professor of dermatology, Harvard Medical School, Boston, at the 2026 annual meeting of the American Academy of Dermatology (AAD). The results were simultaneously published in The New England Journal of Medicine. 

The 30-mg dose of brepocitinib also outperformed placebo in all nine key secondary endpoints. However, 10% of patients in the brepocitinib 30-mg group developed serious infections vs 1% in the placebo group; and 32% of those in the brepocitinib 30-mg group did not reach moderate improvement.

The VALOR trial is a “landmark study in dermatomyositis,” Vleugels said at the meeting. Patients may soon “receive a targeted, effective therapy early in their disease course and avoid systemic corticosteroids and side effects from other traditional DMARDs [disease-modifying antirheumatic drugs] as well,” she added.

Limits of Current Therapy

As the study notes, current therapies for dermatomyositis such as DMARDs and intravenous immune globulin have limited efficacy and toxic effects. They’re also difficult to administer. 

For dermatomyositis, “DMARDs are nonselective and take a very long time to kick in, and often require multiple therapies for patients,” Avery Heather LaChance, MD, associate professor of dermatology, Brigham and Women's Hospital, Boston, who’s familiar with the study findings but was not involved in the research, told Medscape Medical News. 

Inside the Study Design

The study authors note that tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) mediate signal transduction of proinflammatory cytokines linked to dermatomyositis. Brepocitinib inhibits both TYK2 and JAK1. 

The mean age of the study participants was 50.6 years, 77.6% were women, and 68%-77% were White; 81.3% had moderate-to-severe disease activity. All had highly active muscle disease and skin disease.

Patients were allowed to continue stable treatment if they were taking a single antimalarial drug, a single DMARD, or both at baseline. Patients taking systemic glucocorticoids at baseline had to taper the dose to 20 mg or less of a prednisone equivalent per day before they were randomly assigned. However, single brief courses of increased doses of glucocorticoids were allowed from day 1 to week 12, and then more tapering occurred. 

On a skin measurement, the Cutaneous Dermatomyositis Disease Area and Severity Index–Activity (CDASI-A), the researchers tracked improvement in patients with moderate-to-severe skin disease (CDASI-A >14) at baseline. At week 52, the proportion of these patients with cutaneous clinical remission (CDASI-A ≤ 5) was 44% among the 46 patients on the 30-mg dose and 32% among the 47 patients on the 15-mg dose, vs 21% of the 53 patients on placebo.

Adverse Events and Limitations

Adverse event rates were similar across the groups (90% for brepocitinib 30 mg, 86% for brepocitinib 15 mg, and 91% for placebo). The finding regarding serious infections was “consistent with those of other potent immunosuppressants; these events resolved with medical management, and brepocitinib treatment was successfully completed in most cases,” the researchers wrote.

A total of 87.1% of patients completed the trial. Overall, those in the brepocitinib 30-mg group were more likely to discontinue (25%) than those in the placebo group (11%). 

The study highlighted one limitation: a requirement that “background DMARD therapy remain stable throughout the blinded treatment period, even in patients who had marked clinical improvement,” the authors noted. “Although this approach was necessary to ensure an equivalent intensity of background treatment for efficacy assessments, in clinical practice DMARD tapering is common after disease control has been achieved to limit polypharmacy and minimize toxic effects.”

The researchers wrote that data from an ongoing 52-week, open-label extension period will provide more insight into the use of the drug “under more flexible conditions as background therapy.”

‘Very Exciting’ Findings

The findings are “very exciting” and represent a movement toward targeted therapy in dermatomyositis, LaChance said, noting that JAK inhibitors are already used off-label in severe cases. Brepocitinib “will be very helpful and beneficial and a great drug to include for our patients as an option.”

She was especially impressed by improvements in CDASI-A. “This study population had a pretty high burden of skin disease, and the drug showed statistically significant improvement starting at week 4,” she said. 

In contrast, other therapies may take 3-6 months to kick in, she added. 

As for adverse events, LaChance said that the 10% infection rate is not surprising. Once available in the real world, “a question will be whether some of those patients are going to be able to come off their second immune-modulating therapy, and if that infection risk will get lower.”

In regard to cost, LaChance noted that targeted therapies are expensive. But the brepocitinib isn’t likely to be a first-line drug for all patients, she said. And it may have a “significant impact on quality of life” for patients with moderate-to-severe disease.

Priovant Therapeutics funded the trial. Vleugels disclosed relationships with AbbVie, Apogee, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Pfizer, and Priovant. Other study authors reported various and multiple disclosures. LaChance disclosed relationships with Pfizer, Merck, UCB, Priovant, Johnson & Johnson, and Biogen.