Large study documents short-term safety of celecoxib for osteoarthritis

Last Updated: 2006-02-27 8:48:10 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The cyclooxygenase-2 (COX-2) inhibitor celecoxib (Celebrex) causes fewer gastrointestinal complications than traditional nonsteroidal anti-inflammatory drugs (NSAIDs), without raising the risk of cardiovascular thromboembolic events, according to results of a large, prospective, 3-month trial.

Some clinical trials have demonstrated increased cardiovascular risk associated with other COX-2 inhibitors, which led to the withdrawal of two from the market - rofecoxib (Vioxx) and valdecoxib (Bextra). Results of one study suggested that celecoxib, given in large doses (800 mg/day) over prolonged periods of time, may also have a worse cardiovascular risk profile than nonspecific NSAIDs, whereas other studies showed no such risk.

The SUccessive Celecoxib Efficacy and Safety Study-1 (SUCCESS-1), conducted in 39 countries, enrolled 13,194 patients with osteoarthritis of the hip, knee or hand of at least 6 months duration.

The investigators, led by Dr. Gurkirpal Singh from Stanford University School of Medicine in California, randomized patients to celecoxib 100 mg twice daily (n = 4393), celecoxib 200 mg twice daily (n = 4407), naproxen 500 mg twice daily (n = 905), or diclofenac 50 mg twice daily (n = 3489). Treatment duration was 12 weeks.

The researchers report in the American Journal of Medicine for March that all treatments were similarly effective in reducing pain. Moreover, celecoxib 100 mg twice daily was comparable to celecoxib 200 mg twice daily.

The incidence of serious upper gastrointestinal events was 1.0 per 100 patient-years in the NSAID groups and 0.2 per 100 patient-years in the celecoxib groups (odds ratio 6.02, p = 0.004).

Among the 7% of subjects who were using prophylactic aspirin up to 325 mg daily, there were no significant differences in gastrointestinal events between groups. Because of the small number of patients, the authors recommend further controlled studies comparing celecoxib and NSAIDs in aspirin users.

Although numerical differences were seen, there was no statistically significant difference between celecoxib and NSAIDs in any cardiovascular adverse event rate, except that the rate of cardiac failure was higher in the NSAID group (1.00 per 100 patient-years versus 0.22/100 patient-years, odds ratio 4.51, p = 0.01).

When making recommendations for treatment of osteoarthritis, Dr. Singh's group advises, "clinicians should consider a number of factors, including the risk for upper gastrointestinal events, duration of therapy, as well as costs, before deciding upon individual patient treatment."

Am J Med 2006;119:255-266.