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

• Published in: Alimentary pharmacology & therapeutics Vol. 17; no. 2; pp. 201 - 210
• Main Authors: Hunt, R. H., Harper, S., Callegari, P., Yu, C., Quan, H., Evans, J., James, C., Bowen, B., Rashid, F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2003; Blackwell
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - adverse effects; Double-Blind Method; Duodenal Ulcer - chemically induced; Etoricoxib; Female; Gastrointestinal Hemorrhage - chemically induced; Humans; Ibuprofen - adverse effects; Isoenzymes - antagonists & inhibitors; Male; Medical sciences; Membrane Proteins; Middle Aged; Occult Blood; Osteoarthritis - drug therapy; Prostaglandin-Endoperoxide Synthases; Pyridines - adverse effects; Stomach Ulcer - chemically induced; Sulfones - adverse effects
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1046/j.1365-2036.2003.01407.x

Summary Background : Cyclo‐oxygenase‐2‐selective non‐steroidal anti‐inflammatory drugs are intended to preserve cyclo‐oxygenase‐1‐mediated gastroprotection and platelet function, whilst inhibiting cyclo‐oxygenase‐2‐mediated inflammation. Aim : To assess the gastrointestinal safety of the cyclo‐oxygenase‐2‐selective inhibitor etoricoxib vs. non‐selective 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 ≥ 5 mm. 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.