Inhibiting costimulatory activation of T cells : a viable treatment option for rheumatoid arthritis?
There is now good evidence that T cells play a central role in the inflammatory pathway that leads to the persistent synovitis that causes joint damage in rheumatoid arthritis (RA). T cells require two signals to become activated. The second step in the activation of T cells involves costimulatory pathways, the best described pathway being the binding of CD28 on T cells to CD80/86 on antigen-presenting cells. This observation has led to the development of a new category of biological response modifier. Abatacept is a fusion protein (cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin [CTLA4Ig]); which blocks the binding of CD28 by avidly binding CD80/86. Without this costimulatory activation, the T cell becomes anergic. Abatacept has consistently been shown to improve the signs and symptoms of RA in phase II and phase III trials in patients with an inadequate response to methotrexate and anti-tumour necrosis factor (TNF) therapy. Onset of action is rapid and efficacy is maintained during the period of treatment. Recent trials have also provided evidence of improvement in quality-of-life measures and radiographic progression. The safety profile to date has also been favourable and supports the theory that targeting naive T cells early in the inflammatory pathway will lead to immunomodulation rather than immunosuppression. The evidence produced so far suggests that abatacept will be a useful addition to the available therapies for patients with RA.
Pollard
Louise C
LC
Academic Department of Rheumatology, Kings College London, Weston Education Centre, London, UK. louise.pollard@kcl.ac.uk
D000069594:Abatacept; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D018501:Antirheumatic Agents; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept