Biological therapies: A novel approach to the treatment of autoimmune disease

Abstract

Biological therapies for rheumatoid arthritis (RA) make use of molecules (including derivative and recombinant forms) produced by cells of the immune system or by cells that participate in inflammatory reactions. Development of monoclonal antibodies against cell-surface structures that are lineage or subset specific has led to trials of anti-T-cell reagents in RA, but results thus far must be regarded as a significant therapeutic disappointment. A monoclonal antibody designed to interfere with the action of a cytokine, tumor necrosis factor α (TNF-α), has been studied in both open and controlled trials. Treatment with this antibody resulted in marked changes in indices of inflammation, but duration of responses may be limited by the eventual development of antibodies to the anti-TNF-α antibody. Immunomodulatory strategies that use the immune system to regulate autoimmune activity have been developed based on animal studies, and evaluation of oral collagen as a treatment in RA is currently underway. If successful, this approach would represent a new direction in the treatment of human autoimmune disease. In the future, use of gene therapy directed to the joint could be a powerful approach to treatment of RA. Rational use of biological therapies in RA will depend, in part, on improved understanding of the pathogenesis of this condition.