The precise role(s) of cytokines in autoimmune diseases is still being investigated. Several proinflammatory actions of TNF may contribute to its role in the pathogenesis of RA; in addition to stimulating the release of other proinflammatory cytokines, including IL-6, IL-8, IL-1', and leukemia-inhibitory factor (LIF), TNF6 induces the release of proteases from neutrophils, fibroblasts, and chondrocytes. TNF6 also induces expression of endothelial adhesion molecules, which lead to rapid transmigration of leukocytes into extravascular sites. Clinical trials in RA patients using monoclonal antibodies to TNF and soluble TNF receptor fusions proteins have demonstrated remarkable positive clinical improvements in short term trials. The primary objectives of this study are to evaluate the safety, mmunogenicity and pharmacokinetics and potential efficacy of intravenous administration of Recombinant Methionyl Human Tumor Necrosis Factor Binding Protein PEGylated Dimer (TNFbp Dimer) in patients with moderate to severe active rheumatoid arthritis (RA). This will include an assessment of the effect of antibody generation on the clearance of TNFbp Dimer.
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