Drug Insight: abatacept for the treatment of rheumatoid arthritis.
Although the development of tumor necrosis factor antagonists has improved the clinical outcome of many patients with rheumatoid arthritis (RA), some patients fail to respond to these drugs or have contraindications preventing their use. Other approaches for treating this disease are, therefore, keenly sought. As T cells promote numerous disease pathways in RA, these cells are a logical target for anti-inflammatory therapy. One of the approaches being investigated involves targeting the co-stimulatory signals that accompany antigen-derived signals involved in the activation of T cells. Abatacept is a recombinant fusion protein that interrupts the T-cell co-stimulatory signal mediated through the CD28-CD80/CD86 pathway. Several clinical trials have now confirmed the efficacy of this compound in the treatment of RA. This article discusses the proposed mechanism of action of abatacept and reviews the data from phase II and phase III clinical trials on the safety and efficacy of this drug in RA.
Ruderman
Eric M
EM
Division of Rheumatology, Northwestern University Feinberg School of Medicine, 675 North St. Clair Street, Chicago, IL 60611, USA. e-ruderman@northwestern.edu
Pope
Richard M
RM
D000069594:Abatacept; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept