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Selective Costimulation Modulators: Addressing Unmet Needs in Rheumatoid Arthritis Management: Conclusion



Considerable advances in our understanding of the immunologic mechanisms underlying the pathophysiology of RA have led to the recent development of new, targeted biological therapies. The recognition that T cells orchestrate the immune response in RA has prompted the search for therapies that depress activation of T cells. Selective targeting of the CD80/86:CD28 costimulation pathway with agents, such as abatacept, appears to be a particularly attractive approach. Targeting one costimulation pathway, while leaving other pathways controlling T-cell activation largely unaltered, may be the ideal strategy for treating RA and other autoimmune diseases. The clinical trial experience with abatacept suggests that agents that modulate T-cell costimulation pathways provide an effective, safe, and well-tolerated alternative to RA treatments that are currently available. In clinical trials of up to 1 year in duration, abatacept has been shown to significantly improve the clinical signs, functional impairment, and pain associated with RA. Abatacept reduces the severity of RA in patients with varying duration of the disorder and provides additional clinical benefit when used in combination with a synthetic DMARD, such as MTX. Abatacept also appears to be well tolerated, with an adverse event profile in clinical trials that is similar to that of placebo. The low risk of adverse events may make abatacept a good choice for patients with RA who have other comorbidities. Ongoing clinical trials continue to evaluate the role of costimulation blockade in patients for whom anticytokine therapy has failed; these trials will address the effect of costimulation blockade on joint damage.


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