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.
Emery
Paul
P
Academic Unit of Musculoskeletal Disease, Department of Rheumatology, 1st Floor, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX. p.emery@leeds.ac.uk
D000069594:Abatacept; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D018796:Immunoconjugates; D000069594:Abatacept