A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group.
OBJECTIVE
Prostaglandin production in the normal gastrointestinal tract, believed to be critical for mucosal integrity, is mediated by cyclooxygenase (COX)-1, whereas prostaglandin production at inflammatory sites seems to occur via induction of COX-2. We hypothesized that COX-2-specific inhibition with rofecoxib (25 mg once daily) in the treatment of patients with osteoarthritis would cause fewer gastroduodenal ulcers than an equally effective dose of ibuprofen (800 mg 3 times a day), a nonspecific COX inhibitor.


METHODS
A total of 742 osteoarthritis patients without ulcers on baseline endoscopy were randomly assigned to receive rofecoxib (25 or 50 mg once daily), ibuprofen (800 mg 3 times daily), or placebo. Endoscopy was repeated at 6, 12, and 24 weeks. At 16 weeks, by study design, 95% of the placebo group and 5% of the other groups were discontinued.


RESULTS
The cumulative incidence of gastroduodenal ulcers >/=3 mm with rofecoxib (25 or 50 mg once daily) was significantly (P < 0.001) lower than with ibuprofen and was statistically equivalent to placebo at week 12 (placebo, 9.9%; 25 mg rofecoxib, 4.1%; 50 mg rofecoxib, 7.3%; and ibuprofen, 27.7%). At 24 weeks, ulcer rates were 25 mg rofecoxib, 9. 6%; 50 mg rofecoxib, 14.7%; and ibuprofen, 45.8% (P < 0.001, ibuprofen vs. 25 and 50 mg rofecoxib).


CONCLUSIONS
Rofecoxib, at doses 2-4 times the dose demonstrated to relieve symptoms of osteoarthritis, caused significantly less gastroduodenal ulceration than ibuprofen, with ulcer rates comparable to placebo.
Laine
L
L
Division of Gastrointestinal Diseases, University of Southern California, Los Angeles, California, USA. llaine@usc.edu
Harper
S
S
Simon
T
T
Bath
R
R
Johanson
J
J
Schwartz
H
H
Stern
S
S
Quan
H
H
Bolognese
J
J
D000368:Aged; D000369:Aged, 80 and over; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D005773:Gastroscopy; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007527:Isoenzymes / Q000187:drug effects*; D007783:Lactones / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen