COX-2 Inhibitors in Arthritis: Conclusion and References

The discovery of COX-2 and the development of COX-2-selective agents have renewed interest in the role of prostaglandins in the pathogenesis of arthritic illnesses. The complexity of COX-1 and COX-2 functions in normal physiology and pathobiology challenges our understanding of the mechanisms through which both nonselective and COX-2-selective agents act. COX-2 expression in the inflamed synovium of patients with OA and RA suggests that targeting COX-2 may be an effective therapeutic intervention. Limited insight into the normal physiologic roles of COX-2 in the joint, however, leaves unresolved the long-term consequences of unopposed COX-2 inhibition on functions such as bone remodeling and wound healing. The COX-2 agents nonetheless provide the promise of significantly decreased upper GI complications in the long-term treatment of patients with arthritis, raising the hope of alleviating a substantial human and economic cost of morbidity and mortality associated with NSAIDs. This promise extends to benefits of preemptive analgesia, and to an ever-widening arena of treatment potential including Alzheimer's disease and colon cancer. The embrace of COX-2 inhibitors should be appropriately tempered by awareness of cardiovascular and renal implications of unopposed thromboxane A2 production and the effect of diminished prostacyclin on vascular dilation, sodium retention, and platelet aggregation. This caveat is especially important for RA patients, who appear to have a higher incidence of CV events. The needs of patients at high risk for thrombosis or NSAID-related renal toxicity, or patients with ASRD, should be considered carefully. By measures of published clinical experience, COX-2 inhibitors represent a significant advance in the therapy of rheumatic disease. With newer COX-2 agents just over the horizon, treatment options for patients may multiply, expanding the possibility of safe and efficacious therapy for many patients.

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