The adverse gastrointestinal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are well known. In patients who take NSAIDs regularly, upper endoscopic examinations have shown a 15 to 30 percent prevalence of ulcers in the stomach or duodenum. A new class of anti-inflammatory medications has recently been introduced, called cyclooxygenase (COX) inhibitors. NSAIDs inhibit COX, thereby inhibiting prostaglandin production. Two COX enzymes are known to be involved in prostaglandin synthesis, COX-1 and COX-2. COX-1 generates prostaglandins that are involved in the protection of gastrointestinal mucosa, while COX-2 generates prostaglandins that mediate inflammation and pain in sites throughout the body. Selective COX-2 inhibitors may therefore relieve the pain of inflammation without deleterious effects on gastrointestinal mucosa. Laine and associates performed a randomized trial comparing the effect of a COX-2–specific inhibitor (rofecoxib) with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis.

A total of 742 patients with osteoarthritis was randomly assigned to receive rofecoxib (25 or 50 mg once daily), ibuprofen (800 mg three times daily) or placebo. Patients who had evidence of an ulcer on initial endoscopy were excluded. An ulcer was defined as the presence of a mucosal lesion of 3 mm or more. The mean age of the subjects was 62. Approximately two thirds of the patients were women. There was a history of a previous gastrointestinal event in one fifth of the patients. One half of the subjects did not drink alcohol and just over one half smoked. Endoscopy was performed at six, 12 and 24 weeks.

The incidence of gastroduodenal ulcers with rofecoxib therapy was significantly lower than with ibuprofen therapy and was equivalent to placebo. Specifically, ulcers were seen at 12 weeks in 9.9 percent of patients taking placebo, 4.1 percent taking rofecoxib at 25 mg per day, 7.3 percent taking rofecoxib at 50 mg per day, and 27.7 percent taking ibuprofen. The authors then calculated the number-needed-to-treat. At a dosage of 25 mg per day of rofecoxib over six months of treatment, 2.8 patients would need to be treated with rofecoxib rather than ibuprofen to avert the development of an ulcer in one patient.

editor's note: This study confirms the lower rate of gastroduodenal ulcers in patients taking a COX-2 inhibitor. This study did not compare other commonly used NSAIDs or nonacetylated salicylates on the rate of ulcer formation. While it was not the objective of the study to assess analgesic efficacy, it appears that there was no difference between rofecoxib and ibuprofen in this regard. Given the current popularity of COX-2 inhibitors, it will be important to conduct studies that compare the analgesic effect of these medications with those of other NSAIDs, nonacetylated salicylates and appropriate dosages of acetaminophen. This study provides evidence to support the safety of COX-2 inhibitors in the treatment of patients with osteoarthritis.—j.n.