Abatacept could be a new treatment option for people with adult dermatomyositis and polymyositis refractory to conventional treatment, a small, randomized pilot study suggests.

The investigators, led by first author Anna Tjärnlund, PhD , of the Karolinska Institute in Stockholm, noted that the health-related quality of life for people with dermatomyositis (DM) and polymyositis (PM) is low, compared with the general population.

“The majority of commonly used drugs are not approved for myositis, and only [a] few randomized, controlled trials (RCTs) have been performed in this patient group. Thus, there is an unmet need for new therapies for these patients,” they wrote ( Ann Rheum Dis. 2017 Oct 9. doi: 10.1136/annrheumdis-2017-211751 ).

According to the researchers, muscle biopsies of people with DM and PM show a predominance of T cells in inflammatory infiltrates, suggesting a role for T cells in the disease process. Abatacept (Orencia), a fully human fusion protein of CTLA-4 and the Fc portion of human IgG1 that inhibits the co-stimulation of T cells, has been shown in several case reports to have beneficial effects in myositis, but no RCT has been done.

Abatacept is approved by the Food and Drug Administration for the treatment of moderately to severely active rheumatoid arthritis, moderately to severely active polyarticular juvenile idiopathic arthritis, and active psoriatic arthritis in adults.

The aim of the current phase 2b pilot study was to investigate the efficacy and safety of abatacept in a randomized trial with a delayed start in one arm. The researchers randomized 19 patients with DM or PM with refractory disease to receive either immediate active treatment (n = 10) with intravenous abatacept (dosed according to body weight) or a 3-month delayed start (n = 9). Patients who weighed less than 60 kg received 500 mg abatacept, those who weighed 60-100 kg received 750 mg, and those with body weight greater than 100 kg received 1,000 mg.

The primary endpoint was the number of responders defined by the International Myositis Assessment and Clinical Studies (IMACS) Group definition of improvement (relative improvement of 20% or greater in three of any six core set measures, with no more than two core set measures worsening by 25% or more) after 6 months of treatment.

The researchers saw improvements in the active treatment arm, compared with the delayed-start arm. At 3 months, five patients in the active treatment arm were responders, compared with one patient in the delayed treatment arm. For example, the active treatment groups improved by a mean of 2.5 points on the Manual Muscle Testing–8 (one of the individual components of the IMACS core set), compared with –4.9 in the delayed treatment arm (P = .0375).

At 6 months, an intent-to-treat analysis revealed that 8 out of 19 patients responded (2 with DM, 6 with PM) and reached the definition of improvement, with the remaining patients classified as nonresponders.

In patients who had before and after muscle biopsies, the expression of anti-inflammatory Foxp3+ regulatory T cells was significantly greater after abatacept treatment, the researchers reported. They noted that they had previously seen a decrease in the number of Foxp3+ cells in the tissues of patients with myositis on treatment with glucocorticoids.

“This difference could be related to the different treatment targets as since tissue-resident Foxp3+ regulatory T cells have been implicated in muscle repair and regeneration.”

Overall, 36 adverse events were reported during the study. Eight were considered related to abatacept, of which four were considered “mild” and the remaining four “moderate.”

The researchers concluded that although their study was not powered to confirm efficacy, treatment with abatacept was “clinically efficacious in a subgroup of patients with DM or PM and has an acceptable safety profile in refractory patients.”

They cautioned that treatment with abatacept might provide a new treatment option in PM/DM, but it needs to be investigated in randomized, placebo-controlled trials in larger patient populations.

The study was funded by grants from Bristol-Myers Squibb, the Börje Dahlin Foundation, the Swedish Research Council, the Swedish Rheumatism Association, and the King Gustaf V 80-Year Foundation. Two authors reported receiving research grants from Bristol-Myers Squibb and one serves as an advisory board consultant to the company.