Tumor necrosis factor-α blockade in the treatment of rheumatoid arthritis

Tumor necrosis factor-α (TNFα) is a pivotal cytokine in the pathogenesis of rheumatoid arthritis (RA). Several biologic agents have been developed to selectively target this pathogenic element. Infliximab, a chimeric mouse/human antiTNHα monoclonal antibody, has been shown to substantially improve signs and symptoms of RA and inhibit radiologic progression. Etanercept, a genetically engineered molecule comprised of two human 75kd TNF receptorss linked to the Fc portion of human immunoglobulin G, has demonstrated similar efficacy. New agents to block TNFα have been developed, including a fully human antiTNFα monoclonal antibody, a PEGylated humanized antiTNFα fragment, and a PEGylated soluble p55 TNFα receptor. Preclinical data support the combination of TNFα antagonists with agents providing additive or synergistic effects. A number of issues remain unsolved in relation to TNFα antagonists. Despite this, TNFα antagonists have set a new therapeutic standard for RA. Further studies are neglected to clarrify their ultimate position in the therapeutic algorithm.