Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib

SUMMARY Background: Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclooxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. Aim: To assess the gastrointestinal safety of the cyclooxygenase-2-selective inhibitor etoricoxib vs. nonselective non-steroidal anti-inflammatory drugs. Methods: Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric ⁄ duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. Results: In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of ‡ 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of ‡ 5m m. Conclusions: The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds.