Comparison of the upper gastrointestinal safety of Arthrotec (R) 75 and nabumetone in osteoarthritis patients at high risk for developing nonsteroidal anti-inflammatory drug-induced gastrointestinal ulcers

A 6-week, multicenter, double-masked, placebo-controlled, parallel-group st udy compared the upper gastrointestinal (UGI) safety of Arthrotec(R) 75 (di clofenac sodium 75 mg-misoprostol 200 mu g; G.D. Searle & Co., Skokie, Illi nois) administered twice daily with that of nabumetone 1500 mg administered once daily in 1203 patients with symptomatic osteoarthritis (OA) of the hi p or knee. All patients had a documented clinical history of endoscopically confirmed gastric, pyloric-channel, or duodenal ulcer or greater than or e qual to 10 erosions in the stomach or duodenum. UGI endoscopy was performed at baseline and again at week 6 or early withdrawal. Treatment with Arthro tec 75 resulted in a significantly lower combined incidence of endoscopical ly confirmed gastric and duodenal ulcers compared with nabumetone (4% vs 11 %), and its rate of endoscopically confirmed ulceration was equivalent to t hat of placebo. The incidence of gastric ulcers alone was also significantl y lower with Arthrotec 75 than with nabumetone (1% vs 9%). The incidence of duodenal ulcer with Arthrotec 75 was not significantly different from that with nabumetone (4% vs 3%). Types of adverse events were similar for all t reatment groups, with GI adverse events predominating. Arthrotec 75 was wel l tolerated by the majority of patients. The results of this study demonstr ate that Arthrotec 75 has a superior UGI safety profile, causing significan tly fewer UGI ulcers, in comparison with nabumetone in patients with sympto matic OA and a documented history of ulcers or greater than or equal to 10 erosions.