Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandi n production by inhibiting cyclooxygenase (COX); they are believed to cause gastroduodenal damage by inhibiting the COX-1 isoform and to have analgesi c and anti-inflammatory effects by inhibiting the COX-2 isoform. As compare d to conventional NSAIDs, celecoxib, a COX-2 specific inhibitor, has been s hown in previous single posttreatment endoscopy studies to be associated wi th lower gastroduodenal ulcer rates. In response to concerns that such stud ies may under-represent ulceration rates, the present serial endoscopy stud y was designed to compare cumulative gastroduodenal ulcer rates associated with the use of celecoxib to those of naproxen, a conventional NSAID. METHODS: In this double-blind, parallel-group, multicenter study, 537 patie nts with osteoarthritis (OA) or rheumatoid arthritis (RA) were randomized t o treatment with celecoxib 200 mg b.i.d. (n = 270) or naproxen 500 mg b.i.d . (n = 267) for 12 wk. Gastroduodenal damage was determined from esophagoga stroduodenoscopy after 4, 8, and 12 wk of therapy. Arthritis efficacy was e valuated with Patient's and Physician's Global Assessments. RESULTS: Gastroduodenal ulcer rates after celecoxib and naproxen treatment were 4% versus 19% in the 0-4 wk interval (p < 0.001), 2% versus 14% in the 4-8 wk interval (p < 0.001), and 2% versus 14% in the 8-12 wk interval (p < 0.001), respectively. After 12 wk of treatment, the cumulative incidence of gastroduodenal ulcers was 9% with celecoxib and 41% with naproxen. In th e celecoxib group, gastroduodenal ulcers were significantly associated with Helicobacter pylori status (p < 0.05), concurrent aspirin usage (p = 0.001 ), and a history of ulcer (p = 0.010), but not with disease type (OA/RA), a ge, gender. other relevant medical histories, or concurrent corticosteroid or disease-modifying antirheumatic drugs usage (p > 0.05). Celecoxib produc ed a significantly lower incidence rate of both gastric (p < 0.001) and duo denal (p < 0.030) ulcers. The two agents produced similar improvements in P atient's and Physician's Global Assessments of arthritis efficacy. The inci dence of adverse events and withdrawal rates did not differ significantly b etween treatments. CONCLUSIONS: As compared to naproxen (500 mg b.i.d.), use of celecoxib (200 mg b.i.d.), a COX-2 specific agent, at the recommended RA dose and twice t he most frequently prescribed OA dose, was associated with lower rates of g astric, duodenal, and gastroduodenal ulcers but had comparable efficacy, in patients with OA and RA. (Am J Gastroenterol 2001;96:1019-1027. (C) 2001 b y Am. Coll. of Gastroenterology).