Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin production by inhibiting cyclooxygenase (COX); they are believed to cause gastroduodenal damage by inhibiting the COX-1 isoform and to have analgesic and anti-inflammatory effects by inhibiting the COX-2 isoform. As compared to conventional NSAIDs, celecoxib, a COX-2 specific inhibitor, has been shown in previous single posttreatment endoscopy studies to be associated with lower gastroduodenal ulcer rates. In response to concerns that such studies may under-represent ulceration rates, the present serial endoscopy study 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 patients with osteoarthritis (OA) or rheumatoid arthritis (RA) were randomized to 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 esophagogastroduodenoscopy after 4, 8, and 12 wk of therapy. Arthritis efficacy was evaluated 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 10% 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 the 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), age, gender, other relevant medical histories, or concurrent corticosteroid or disease-modifying antirheumatic drugs usage (p > 0.05). Celecoxib produced a significantly lower incidence rate of both gastric (p < 0.001) and duodenal (p < 0.030) ulcers. The two agents produced similar improvements in Patient's and Physician's Global Assessments of arthritis efficacy. The incidence of adverse events and withdrawal rates did not differ significantly between 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 the most frequently prescribed OA dose, was associated with lower rates of gastric, duodenal, and gastroduodenal ulcers but had comparable efficacy, in patients with OA and RA.