A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucose of patients with osteoarthritis

Background & Aims: Prostaglandin production in the normal gastrointestinal tract, believed to be critical for mucosal integrity, is mediated by cycloo xygenase (COX)-1, whereas prostaglandin production at inflammatory sites se ems to occur via induction of COX-2. We hypothesized that COX-2-specific in hibition with rofecoxib (25 mg once daily) in the treatment of patients wit h osteoarthritis would cause fewer gastroduodenal ulcers than an equally ef fective dose of ibuprofen (800 mg 3 times a day), a nonspecific COX inhibit or. Methods: A total of 742 osteoarthritis patients without ulcers on basel ine endoscopy were randomly assigned to receive rofecoxib (25 or 50 mg once daily), ibuprofen (800 mg 3 times daily), or placebo. Endoscopy was repeat ed at 6, 12, and 24 weeks. At 16 weeks, by study design, 95% of the placebo group and 5% of the other groups were discontinued. Results: The cumulativ e incidence of gastroduodenal ulcers greater than or equal to 3 mm with rof ecoxib (25 or 50 mg once daily) was significantly (P < 0.001) lower than wi th ibuprofen and was statistically equivalent to placebo at week 12 (placeb o, 9.9%; 25 mg rofecoxib, 4.1%; 50 mg rofecoxib, 7.3%; and ibuprofen, 27.7% ). At 24 weeks, ulcer rates were 25 mg rofecoxib, 9.6%; 50 mg rofecoxib, 14 .7%; and ibuprofen, 45.8% (P < 0.001, ibuprofen vs. 25 and 50 mg rofecoxib) . Conclusions: Rofecoxib, at doses 2-4 times the dose demonstrated to relie ve symptoms of osteoarthritis, caused significantly less gastroduodenal ulc eration than ibuprofen, with ulcer rates comparable to placebo.