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


OBJECTIVE
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 > or = 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 > or = 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.
Hunt
R H
RH
Division of Gastroenterology, McMaster University Medical Center, Hamilton, Ontario, Canada. huntr@mcmaster.ca
Harper
S
S
Callegari
P
P
Yu
C
C
Quan
H
H
Evans
J
J
James
C
C
Bowen
B
B
Rashid
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D004381:Duodenal Ulcer / Q000139:chemically induced*; D000077613:Etoricoxib; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009780:Occult Blood; D010003:Osteoarthritis / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases; D011725:Pyridines / Q000009:adverse effects*; D013276:Stomach Ulcer / Q000139:chemically induced*; D013450:Sulfones / Q000009:adverse effects*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011725:Pyridines; D013450:Sulfones; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen; D000077613:Etoricoxib