Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis - A randomized controlled trial

Context In vitro studies have shown that celecoxib inhibits cyclooxygenase 2 (COX-2) but not COX-1, suggesting that this drug may have anti-inflammato ry and analgesic activity without adverse upper gastrointestinal (GI) tract effects that result from COX-1 inhibition. Objective To test whether celecoxib has efficacy as an anti inflammatory an d analgesic with reduced GI tract mucosal damage compared with conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis . Design Randomized, multicenter, placebo-controlled, double-blind trial last ing 12 weeks, with follow-up at weeks 2, 6, and 12, from September 1996 thr ough February 1998, Setting Seventy-nine clinical sites in the United States and Canada. Patients A total of 1149 patients aged 18 years or older with symptomatic r heumatoid arthritis who met inclusion criteria were randomized; 688 (60%) o f these completed the study. Interventions Patients were randomized to receive celecoxib, 100 mg, 200 mg , or 400 mg twice per day (n = 240, 235, and 218, respectively); naproxen, 500 mg twice per day (n = 225); or placebo (n = 231). Main Outcome Measures Improvement in signs and symptoms of rheumatoid arthr itis as assessed using standard measures of efficacy and GI tract safety as assessed by upper GI tract endoscopy before and after treatment, compared among treatment groups. Results All dosages of celecoxib and naproxen significantly improved the si gns and symptoms of arthritis compared with placebo. Maximal anti-inflammat ory and analgesic activity was evident within 2 weeks of initiating treatme nt and was sustained throughout the 12 weeks. The incidence of endoscopical ly determined gastroduodenal ulcers in placebo-treated patients was 4 (4%) of 99, and the incidences across all dosages of celecoxib were not signific antly different (P>.40): 9 (6%) of 148 with 100 mg twice per day, 6 (4%) of 145 with 200 mg twice per day, and 8 (6%) of 130 with 400 mg twice per day . In contrast, the incidence with naproxen was 36 (26%) of 137, significant ly greater than either placebo or celecoxib (P<.001). The overall incidence s of GI tract adverse effects were 19% for placebo; 28%, 25%, and 26% for c elecoxib 100 mg, 200 mg, and 400 mg twice per day, respectively; and 31% fo r naproxen. Conclusion In this study, all dosages of celecoxib were efficacious in the treatment of rheumatoid arthritis and did not affect COX-1 activity in the GI tract mucosa as evidenced by less frequent incidence of endoscopic ulcer s compared with naproxen.