Abstract
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.
Key Points
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T-cell activation requires an antigen-specific interaction between the T-cell receptor and the major histocompatability complex, and a second, co-stimulatory signal
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The interaction between CD28 on the T cell and CD80 or CD86 on the antigen-presenting cell provides one of the most important co-stimulatory signals
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Abatacept, a fusion protein containing components of IgG and cytotoxic T-lymphocyte-associated protein 4, can interrupt the CD28–CD80/CD86 interaction
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Clinical trials have shown that abatacept is an effective agent in patients with rheumatoid arthritis who have failed to respond to treatment with methotrexate or tumor necrosis factor antagonists
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Dr Ruderman has received research grants and consulting fees (totalling less than $5,000) from Bristol-Meyers Squibb. Dr Pope has declared no competing interests.
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Ruderman, E., Pope, R. Drug Insight: abatacept for the treatment of rheumatoid arthritis. Nat Rev Rheumatol 2, 654–660 (2006). https://doi.org/10.1038/ncprheum0345
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DOI: https://doi.org/10.1038/ncprheum0345
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