Clinical experience with cyclooxygenase-2 inhibitors

Abstract

Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic conditions requiring long‐term therapy for pain relief. Currently prescribed non‐steroidal anti‐inflammatory drugs (NSAIDs) provide symptomatic efficacy, but are frequently associated with gastrointestinal (GI) toxicities such as dyspepsia and ulcerations. In a small but significant number of cases, complications including perforations and massive bleeding develop and these may be fatal. A desirable therapeutic strategy would maintain efficacy while minimizing gastric intolerance. Two potential approaches have been suggested: (i) administration of NSAIDs in combination with gastroprotective compounds; or (ii) administration of potentially safer anti‐inflammatory compounds which act via selective inhibition of cyclooxygenase‐2 (COX‐2). The selective COX‐2 inhibitors rofecoxib and celecoxib consistently demonstrate efficacy comparable to conventional NSAIDs in patients with RA and OA, but have a significantly reduced propensity to cause GI toxicity. In many cases, the gastric effects of therapeutically active doses of COX‐2 inhibitors are indistinguishable from placebo. The safety benefits of COX‐2 inhibitors given alone appear similar to combined therapy with conventional NSAIDs and gastroprotective agents. Findings warrant the consideration of COX‐2 inhibitors as first‐line therapy in patients requiring long‐term pain relief.