Celecoxib

Paul L. McCormack

Celecoxib (Celebrex®) was the first cyclo-oxygenase (COX)-2 selective inhibitor (coxib) to be introduced into clinical practice. Coxibs were developed to provide anti-inflammatory/analgesic activity similar to that of nonselective NSAIDs, but without their upper gastrointestinal (GI) toxicity, which is thought to result largely from COX-1 inhibition. Celecoxib is indicated in the EU for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults. This article reviews the clinical efficacy and tolerability of celecoxib in these EU-approved indications, as well as overviewing its pharmacological properties. In randomized controlled trials, celecoxib, at the recommended dosages of 200 or 400 mg/day, was significantly more effective than placebo, at least as effective as or more effective than paracetamol (acetaminophen) and as effective as nonselective NSAIDs and the coxibs etoricoxib and lumiracoxib for the symptomatic treatment of patients with active osteoarthritis, rheumatoid arthritis or ankylosing spondylitis. Celecoxib was generally well tolerated, with mild to moderate upper GI complaints being the most common body system adverse events. In meta-analyses and large safety studies, the incidence of upper GI ulcer complications with recommended dosages of celecoxib was significantly lower than that with nonselective NSAIDs and similar to that with paracetamol and other coxibs. However, concomitant administration of celecoxib with low-dose cardioprotective aspirin often appeared to negate the GI-sparing advantages of celecoxib over NSAIDs. Although one polyp prevention trial noted a dose-related increase in cardiovascular risk with celecoxib 400 and 800 mg/day, other trials have not found any significant difference in cardiovascular risk between celecoxib and placebo or nonselective NSAIDs. Meta-analyses and database-derived analyses are inconsistent regarding cardiovascular risk. At recommended dosages, the risks of increased thrombotic cardiovascular events, or renovascular, hepatic or hypersensitivity reactions with celecoxib would appear to be small and similar to those with NSAIDs. Celecoxib would appear to be a useful option for therapy in patients at high risk for NSAID-induced GI toxicity, or in those responding suboptimally to or intolerant of NSAIDs. To minimize any risk, particularly the cardiovascular risk, celecoxib, like all coxibs and NSAIDs, should be used at the lowest effective dosage for the shortest possible duration after a careful evaluation of the GI, cardiovascular and renal risks of the individual patient.