Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group.
OBJECTIVE
This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design).


METHODS
Seven hundred seventy-five patients with osteoarthritis were randomized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibuprofen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assessed by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks, respectively.


RESULTS
Ulcers were significantly less common (P < 0.001) following treatment with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3% and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 46.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence.


CONCLUSIONS
At 2-4 times the therapeutically effective dose, rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen. Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied prespecified criteria for equivalence to placebo.
Hawkey
C
C
University Hospital Queen's Medical Centre, Nottingham, UK.
Laine
L
L
Simon
T
T
Beaulieu
A
A
Maldonado-Cocco
J
J
Acevedo
E
E
Shahane
A
A
Quan
H
H
Bolognese
J
J
Mortensen
E
E
D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000453:epidemiology; D004386:Duodenum; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects; D015994:Incidence; D007413:Intestinal Mucosa / Q000187:drug effects*; D007783:Lactones / Q000009:adverse effects / Q000494:pharmacology*; D010919:Placebos; D013450:Sulfones
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007783:Lactones; D010919:Placebos; D013450:Sulfones; C116926:rofecoxib; D007052:Ibuprofen