title: 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.
abstract: 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.
authors.affiliation: Division of Gastrointestinal Diseases, University of Southern California, Los Angeles, California, USA. llaine@usc.edu
authors.forename: L
authors.initials: L
authors.lastname: Laine
authors.forename: S
authors.initials: S
authors.lastname: Harper
authors.forename: T
authors.initials: T
authors.lastname: Simon
authors.forename: R
authors.initials: R
authors.lastname: Bath
authors.forename: J
authors.initials: J
authors.lastname: Johanson
authors.forename: H
authors.initials: H
authors.lastname: Schwartz
authors.forename: S
authors.initials: S
authors.lastname: Stern
authors.forename: H
authors.initials: H
authors.lastname: Quan
authors.forename: J
authors.initials: J
authors.lastname: Bolognese
mesh_terms: 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
chemical_list: 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