Incidence of gastroduodenal ulcers associated with valdecoxib compared with that of ibuprofen and diclofenac in patients with osteoarthritis.
OBJECTIVE
To determine whether valdecoxib, at chronic arthritis doses, has the characteristics of a cyclo-oxygenase 2 (COX-2) specific inhibitor, as measured by a reduced incidence of upper-gastrointestinal ulceration compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs).


METHODS
This double-blind, multicentre, placebo-controlled, parallel-group study compared the incidence of gastroduodenal ulcers associated with valdecoxib 10 mg daily (q.d.) and 20 mg q.d. with that of ibuprofen 800 mg three times daily (t.i.d.) or diclofenac 75 mg twice daily (b.i.d.) when administered over a 12-week period. The incidence of gastroduodenal ulcers was assessed by upper-gastrointestinal endoscopy, performed at baseline and again at the end of week 12 (or at early study termination). Efficacy assessments were performed at baseline and at weeks 2, 6 and 12 using Patient's and Physician's Global Assessments of Arthritis.


RESULTS
A total of 1052 osteoarthritis patients were enrolled into the trial. The incidence of gastroduodenal ulcers over 12 weeks was 5% in patients receiving valdecoxib 10 mg q.d., 4% in patients receiving valdecoxib 20 mg q.d., 7% in patients receiving placebo, 16% in patients receiving ibuprofen 800 mg t.i.d. (P <0.05 v. placebo), and 17% in patients receiving diclofenac 75 mg b.i.d. (P <0.05 v. placebo). The incidence of gastroduodenal ulcers at week 12 seen in the ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. groups was significantly higher than that in the valdecoxib 10 mg q.d. and valdecoxib 20 mg q.d. groups (P <0.05). The incidence rates of gastroduodenal ulcers were not significantly different between the valdecoxib treatment groups or between valdecoxib- and placebo-treated patients. Efficacy responses to valdecoxib 10 mg and 20 mg q.d. were significantly greater than placebo and comparable with both ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d.


CONCLUSIONS
The results of the study demonstrate that valdecoxib has an upper-gastrointestinal safety profile typical of a COX-2 specific inhibitor. Overall, the data indicate that administration of valdecoxib offers similar efficacy for the treatment of osteoarthritis but improved upper-gastrointestinal safety compared with the conventional NSAIDs, ibuprofen and diclofenac, based on the significantly lower incidence of gastroduodenal ulcers detected by endoscopy.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D051546:Cyclooxygenase 2; D004008:Diclofenac / Q000009:adverse effects*; D004311:Double-Blind Method; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000382:microbiology; D005260:Female; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007555:Isoxazoles / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000382:microbiology; D011451:Prostaglandin-Endoperoxide Synthases; D013276:Stomach Ulcer / Q000139:chemically induced / Q000382:microbiology; D013449:Sulfonamides / Q000009:adverse effects*; D016896:Treatment Outcome; D000096926:Benzenesulfonamides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051546:Cyclooxygenase 2; D004008:Diclofenac; D007052:Ibuprofen; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human