Abatacept Shows Promise for Some Myositis Patients

An isolated T cell. Abatacept is a selective T cell costimulation modulator.

Injected abatacept may be a worthwhile treatment for certain patients with idiopathic inflammatory myositis (IIM), according to recent research.¹ Patients with the rare autoimmune conditions involving inflammation of muscle (myositis) and other organ systems suffer widespread organ dysfunction, increased morbidity, physical disabilities and early death. Symptoms vary by subtype. For example, dermatomyositis (DM) involves muscle weakness and skin rash on the face and joints; polymyositis (PM) does not. Immune-mediated necrotizing myopathy (IMNM) is a severe form of the disease marked by rapid muscle breakdown. Standard treatment for IIM is often the glucocorticoid prednisone, which has many side effects because it is given at high doses for long periods. Other common treatments include methotrexate or azathioprine, and gammaglobulin.

The phase 3 clinical trial of abatacept, commonly used to treat rheumatoid arthritis, in the treatment of patients with IIM shows the drug may present an alternative for some patients. Patients with PM and IMNM experienced benefit from injected abatacept that was sustained for a year, when added to standard therapy, with no new safety concerns.

But abatacept is not a first-line treatment. “I do advise that if you have a [patient with] necrotizing myopathy [for whom traditional first-or second-line immunosuppressive therapies [have failed to work] then it is reasonable to consider abatacept,” says Rohit Aggarwal, MD, professor of medicine at the University of Pittsburgh, associate director of the University of Pittsburgh Myositis Center, program director of the UPMC Myositis Fellowship Program and the paper’s first author.

Why Study Abatacept?

The U.S. Food & Drug Administration (FDA) has approved no drugs for IIM tested in phase 3, randomized trials. The FDA approved prednisone and adrenocorticotropic hormone in the 1950s, but to this day little data exist to suggest it is effective and safe for patients with myositis, Dr. Aggarwal notes.

He studied abatacept because “it had strong biological plausibility and rheumatologists have safety experience with it.” Abatacept blocks B and T cell interaction and prevents T cell activation. In myopathies, certain T cells infiltrate muscle tissue and damage it, and B cells produce autoantibodies that exacerbate the immune response, leading to destroyed muscle tissue. Meanwhile, a small phase 2 trial found that treatment with abatacept was associated with significant improvement of disease activity in almost half of adult patients with DM and PM, with an acceptable safety profile.²