Abatacept: the first T lymphocyte co-stimulation modulator, for the treatment of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a multisystem autoimmune disease, of unknown aetiology with high morbidity and significantly increased mortality. Over recent years, the introduction of targeted therapies with biologic agents have made major inroads to the outcomes in RA. The first such agents developed were TNF-alpha inhibitors. However, despite their high efficacy, up to 30% patients fail to respond adequately, or develop adverse reaction to TNF-alpha inhibitors. This suggests that other pathological mechanisms are involved, in addition to those mediated by TNF-alpha. Abnormal T-cell function has long been thought to play a key role in the pathogenesis of RA, stimulating both the production of pro-inflammatory cytokines and recruitment of other inflammatory cells, resulting in joint destruction and systemic disease. Abatacept, the first of a group of T-cell co-stimulation modulators, targeting T-cell activation, has recently been licensed for use in RA and shows promise as a useful drug to treat this major disabling disease.