Tumor necrosis factor-alpha (TNF-a) inhibitors may be useful for the treatment of some cases of refractory dermatomyositis and polymyositis (DM/PM), according to a small retrospective study published in the online edition of the Annals of Rheumatic Diseases.¹

In the study, eight patients with DM/PM who had failed treatment with corticosteroids, intravenous gamma globulin (IVIG), and immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil, and leflunomide) were treated with TNF inhibitors as adjunct therapy. Specifically, six patients were treated with etanercept alone, one with infliximab and one patient sequentially with both anti-TNF-a agents. On average, study patients had DM/PM for about 8.5 (± 4.4) (mean ± SD) years before initiating biologic therapy.

Six out of the eight patients in the study had a favorable response, with improved motor strength and decreased fatigue after 15.2 (± 6.5) months of therapy, the study showed. Two patients did not respond after 4 (± 1.4) months, and as a result, TNF inhibitors were discontinued. Responders experienced a 54.4 (± 27.7)% decrease in serum creatine kinase (CK) levels, which were initially grossly abnormal. Nonresponders had similar CK reductions, but their pretreatment levels were within the normal range, suggesting that serum CK levels may help guide the selection of patients who would benefit from anti-TNF therapies.

DM/PM patients with "inflammatory phenotype" may be best candidates

"Our experience suggests that the patients that will benefit the most are the ones that have high baseline serum levels of muscle enzymes, possibly suggesting a more ‘inflammatory phenotype,' whereas TNF may have a more significant role in the propagation of inflammation," says lead researcher Petros Efthimiou, MD, of the division of allergy, immunology, and rheumatology at New Jersey Medical School, University of Medicine and Dentistry of New Jersey, in Newark, New Jersey. "Therefore, careful selection of patients is needed for these agents to demonstrate efficacy," he suggests.

"I believe that the initial approach in cases of resistant DM/PM cases should be a step back and re-evaluation of the case," Dr. Efthimiou advises. "There are genetic disorders (eg, dysferlinopathy) that can mimic inflammatory myopathies and, unless specifically looked for, can remain undiagnosed. If these disorders are ruled out and it is a true case of resistant DM/PM, then it is reasonable to add a TNF inhibitor in the therapeutic regimen."

Going forward, "larger, controlled studies are needed," says Dr. Efthimiou, adding that there is an ongoing study of infliximab in inflammatory myopathies at NIAMS (NIH), and a pilot study of etanercept in the treatment of DM/PM may start soon in Boston.

Reference

1. Efthimiou P, Schwartzman S, Kagen L. Possible role for TNF-inhibitors in the treatment of resistant sermatomyositis and polymyositis. Ann Rheum Dis. [serial online]. February 13, 2006;doi.10.1136/ard.2005.048744.