Celecoxib is just as effective as naproxen and diclofenac for treating osteoarthritis, and it causes significantly fewer serious upper GI events than the other agents, according to data from a large international study.
The finding “shows conclusively that celecoxib does reduce the risk of upper GI complications, compared to conventional NSAIDs,” the study's lead author, Dr. Gurkirpal Singh, said in an interview. “Until now managed care has been saying there is no evidence in a randomized, clinical trial that celecoxib is better than NSAIDs in reducing GI bleeding. But here it is—these are level 1 data that conclusively prove that.”
However, Dr. Brennan M.R. Spiegel noted that although the difference favoring celecoxib reached significance, the actual difference was only 1 patient per 100 patient-years. This tiny difference “is not enough to warrant spending as much as we do on Cox-2 inhibitors,” said Dr. Spiegel of the digestive diseases division at the University of California, Los Angeles. He added that the study is “notable because it's very large, [but] I believed it before that GI events are less common with coxibs than with NSAIDs.”
In a trial called the Successive Celecoxib Efficacy and Safety Study-1 (SUCCESS-1), Dr. Singh and his associates randomized 13,194 osteoarthritis (OA) patients from 39 countries to double-blinded treatment with celecoxib 100 mg b.i.d., celecoxib 200 mg b.i.d., or nonselective NSAID therapy for 12 weeks. The NSAID therapy consisted of diclofenac 50 mg b.i.d. or naproxen 500 mg b.i.d. (Am. J. Med. 2006; 119:255–66).
Patients with a history of two or more episodes of active peptic ulceration were excluded from the study, as were those with GI bleeding or recurrent gastric or duodenal ulcers and those with an esophageal, gastric, or duodenal ulcer within a month prior to randomization. Patients with active GI disease or any condition that required NSAID therapy were also excluded.
Participants' mean age was 62 years, 76% were women, and 80% were white, reported Dr. Singh of the division of gastroenterology and hepatology at Stanford (Calif.) University. The mean duration of OA was 8 years.
Instruments used to measure efficacy included the Patient's Assessment of Arthritis Pain-Visual Analog Scale, Patients' Global Assessment of Arthritis, and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. Serious GI events were evaluated by two independent committees that were blinded to patient randomization.
The researchers reported that the primary efficacy measures showed that both doses of celecoxib were equally as effective as the NSAIDs in treating OA.
There were 37 confirmed upper GI events: 19 in the patients who took the NSAIDs and 18 in the patients who took celecoxib. That translated into a rate of 2.1 per 100 patient-years for patients who took the NSAIDS vs. a rate of 1.0 per 100 patient-years for those who took celecoxib. The difference was statistically significant.
A key limitation of the study, Dr. Singh said, is that it was not powered to detect differences in cardiovascular adverse events.
Dr. Spiegel said that the current standard of care for older patients with OA has “overtaken” the overall impact of the SUCCESS-1 study findings. “The reality is that people are moving to adding a proton pump inhibitor to an NSAID when [osteoarthritis] patients exceed the age of 65 or if they're put on aspirin,” he said.
Dr. Singh disclosed that he received research support from Searle Pharmaceuticals, Pharmacia, Pfizer, Merck & Co., Boehringer Ingelheim, TAP Pharmaceuticals, Wyeth, Altana Pharma, GlaxoSmithKline, Novartis Pharmaceuticals Corp., and Centocor Inc.
'Celecoxib does reduce the risk of upper GI complications, compared to conventional NSAIDs.' DR. SINGH