Abstract

Blocking the effect of interleukin-1 and tumor necrosis factor in rheumatoid arthritis is well-tolerated and effective

Author(s): Roy M Fleischmann

Interleukin (IL)-1 is a primary mediator in the pathophysiology of rheumatoid arthritis. Elevated IL-1 levels have been detected in the synovium of patients with rheumatoid arthritis and such elevated levels have been correlated with disease severity. In animal models, overexpression of IL-1 produces pathology closely resembling rheumatoid arthritis in humans. IL-1 receptor antagonist is an endogenous IL-1 antagonist. Genetically altered mice, designed to be deficient in IL-1 receptor antagonist, spontaneously develop a condition similar to rheumatoid arthritis. Anakinra is a recombinant human IL-1 receptor antagonist approved by the US Food and Drug Administration as a therapy for patients with rheumatoid arthritis. In clinical trials, patients receiving anakinra were more likely to achieve a higher response, as evaluated by the American College of Rheumatology criteria, than patients receiving placebo. Radiologic evaluation indicated a statistically significant slowing of cartilage destruction. Patients treated with a combination of methotrexate and anakinra demonstrated statistically significant improvements in American College of Rheumatology responses and slowing of x-ray progression compared with patients receiving methotrexate alone. Anakinra has been shown to be relatively nontoxic in animal studies and is well tolerated by most patients. The most frequent adverse event is injection site reaction. Anakinra therapy is an effective and well-tolerated treatment for rheumatoid arthritis. In clinical practice, its emerging role is to treat patients who have discontinued therapy with one or more of the agents that block tumor necrosis factor or in patients who have a contraindication to such agents.