The therapeutic potential of costimulatory blockade with CTLA4Ig in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterised by joint inflammation and destruction. Controversy exists regarding the significance and exact role of activated T cells in RA. CTLA4Ig is a soluble fusion protein (cytotoxic T lymphocyte-associated antigen 4 fused to the heavy chain constant region of human IgG1), which represents the first in a new class of agents called costimulation blockers. By blocking the second signal required for optimal T-cell activation, CTLA4Ig has demonstrated efficacy in a variety of spontaneous and induced animal models of autoimmunity. A Phase II clinical study in RA showed CTLA4Ig was efficacious with an acceptable safety profile. These results suggest that activated T cells may be important in RA pathogenesis and that costimulation blockade may be a novel therapeutic approach for this disorder.