The use of TNF-? blocking agents in rheumatoid arthritis: an overview

Abstract

TNF-α has been found to play a pivotal role in the pathogenic mechanisms of rheumatoid arthritis (RA). The overexpression of TNF-α in RA synovium, the data from in vitro synovial cell cultures with the use of anti-TNF-α antibody and the results from TNF-α blockade in animal models of arthritis argued for the importance of this cytokine in RA. Drugs targeting TNF-α have been developed to neutralise the deleterious effects of this inflammatory cytokine. There are currently three drugs available in the treatment of RA patients with active disease, which was refractory to conventional treatments including methotrexate, infliximab (a chimeric mouse/human monoclonal antibody), etanercept (a fusion protein combining 2 p75 TNF receptors with a Fc fragment of human IgG1) and adalimumab (a fully human monoclonal antibody). These three drugs have proved to be effective and safe in appropriate and well conducted clinical trials and showed effectiveness in slowing and even arresting the progression of radiographic damage. With the long-term surveillance of these drugs serious adverse events were described, particularly intracellular organism infections such as tuberculosis. Other drugs targeting TNF-α are in development and include monoclonal antibody (CDP571), pegylated molecules (CDP870 and PEG-r-Hu-sTNF-RI) or soluble p55 TNF receptor construct (lenercept). These new biological therapies blocking TNF-α undoubtedly constitute a considerable advance in the management of RA, but careful evaluation at the initiation of the treatment and long-term surveillance of the patients receiving such drugs remains necessary.