Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis - A randomized, double-blind, placebo-controlled trial

This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastro duodenal ulcers than ibuprofen tin a multicenter trial), and its side effec ts would be equivalent to those of placebo tin a prespecified analysis comb ining the results with another trial of identical design). Methods. Seven hundred seventy-five patients with osteoarthritis were rando mized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibupro fen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assesse d by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary a nd secondary end points were the incidence of gastroduodenal ulcers at 12 a nd 24 weeks, respectively. Results. Ulcers were significantly less common (P < 0.001) following treatm ent with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3 % and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 4 6.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence. Conclusion. At 2-4 times the therapeutically effective dose, rofecoxib caus ed fewer endoscopically detected ulcers than did ibuprofen, Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied p respecified criteria for equivalence to placebo.