Developing a New Generation of TNFα Antagonists for the Treatment of Rheumatoid Arthritis

Abstract

The convergence of three research pathways has led to the development of a new class of biological agents that can successfully treat chronic disease, including aggressive rheumatoid arthritis (RA). Basic studies on the pathogenesis of RA identified tumor necrosis factor–α (TNFα ) as the central mediator of the chronic inflammation that results in joint swelling, degradation, and loss of function. Parallel development of monoclonal antibody (MAb) and recombinant DNA technologies has enabled the design and production of several potent biologics that can specifically block the deleterious effects of TNFα . Two MAbs (infliximab and adalimumab), as well as a receptor fusion protein (etanercept), have thus far proven safe and efficacious in pivotal RA clinical trials. These evolving technologies provide the foundation from which future biotherapies can be derived as targets are identified and validated in diverse disease states.