Biologic agents in the therapy of inflammatory rheumatic diseases, including therapeutic antibodies, cytokines, and cytokine antagonists

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Abstract
As a result of a better understanding of the mechanisms that underlie diseases such as rheumatoid arthritis, biologic agents have been used increasingly in the therapy of inflammatory rheumatic diseases. Monoclonal antibodies directed against either cell surface constituents mainly on CD4+ T cells or cytokines such as tumor necrosis factor-alpha, fusion toxins reactive with cell activation membrane markers, and cytokine inhibitors, have been shown to be safe and possibly efficacious in open trials. At present, most ongoing studies are focused on the treatment of refractory rheumatoid arthritis and lupus nephritis. Open therapeutic trials are followed by double-blind placebo-controlled phase II and III studies, which are necessary to prove the efficacy of the various biologic agents. Open trials, however, already have shown that only a short decrease in the inflammatory activity of arthritis can be induced and that anti-idiotypic and human anti-mouse antibodies are induced even when humanized monoclonal antibodies are used. Nevertheless, a significant improvement in the available therapeutic repertoire for the treatment of inflammatory rheumatic diseases is expected.

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