Current issues of ACP Journal Club are published in Annals of Internal Medicine


Rofecoxib caused fewer endoscopic gastroduodenal ulcers than ibuprofen in osteoarthritis


ACP J Club. 2000 May-June;132:96. doi:10.7326/ACPJC-2000-132-3-096

Related Content in this Issue
• Companion Abstract and Commentary: Celecoxib was similar to naproxen for rheumatoid arthritis with fewer endoscopic ulcers

Source Citation

Laine L, Harper S, Simon T, et al., for the Rofecoxib Osteoarthritis Endoscopy Study Group. 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. Gastroenterology. 1999 Oct;117:776-83. [PubMed ID: 10500058]



In patients with osteoarthritis (OA), does rofecoxib at doses of 25 and 50 mg/d cause fewer endoscopic gastroduodenal ulcers than ibuprofen?


Randomized (allocation concealed*), blinded (patients, clinicians, and outcome assessors),* placebo-controlled trial with 24-week follow-up.


33 clinical centers in the United States.


742 patients (mean age 62 y, 68% women, 83% white) ≥ 50 years of age with OA that had required nonsteroidal anti-inflammatory drugs (NSAIDs) for ≥ 6 months. Exclusion criteria were active ulcers; inflammatory bowel disease; previous upper gastrointestinal (GI) surgery; pyloric obstruction; erosive esophagitis; abnormal serum creatinine levels or clearance; fecal occult blood; unstable medical conditions; history of cancer or cerebrovascular events; bleeding diathesis; or need for anticoagulants, ticlopidine, corticosteroids, or aspirin. The intention-to-treat analysis included 93% of the patients.


Patients were allocated to 16 to 24 weeks of rofecoxib, 25 mg/d (n = 195); rofecoxib, 50 mg/d (n = 186); ibuprofen, 2400 mg/d (n = 184); or placebo (n = 177). Some other drugs were allowed (acetaminophen, non-NSAIDs, and an antacid [Gelusil]).

Main outcome measures

Endoscopic gastroduodenal ulcers ≥ 3 mm at 12 weeks (primary outcome) and 24 weeks (secondary outcome). A similar analysis was done with ulcers ≥ 5 mm at 12 and 24 weeks.

Main results

Patients in the rofecoxib groups and the placebo group had lower rates of endoscopic ulcers of both sizes than did patients in the ibuprofen group at 12 weeks (Table); patients in both rofecoxib groups also had lower rates of endoscopic ulcers of both sizes at 24 weeks (P < 0.001 for comparisons with ibuprofen). The rofecoxib and placebo groups did not differ for any outcome. Rofecoxib and ibuprofen had similar efficacy.


Rofecoxib, 25 or 50 mg/d, and placebo had lower rates of endoscopic gastroduodenal ulcers than did ibuprofen in patients with osteoarthritis.

Source of funding: Merck & Co., Inc.

For correspondence: Dr. L. Laine, GI Liver Division, Department of Medicine (LAC 12-137), University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033, USA. FAX 323-226-7573.

Table. Endoscopic gastroduodenal ulcers ≥ 3 mm with rofecoxib and placebo vs ibuprofen for osteoarthritis†

Comparison at 12 wk Event rates RRR (95% CI) NNT (CI)
Rofecoxib, 25 mg/d, vs ibuprofen 4% vs 25% 85% (68 to 93) 5 (3 to 7)
Rofecoxib, 50 mg/d, vs ibuprofen 7% vs 25% 73% (52 to 85) 5 (4 to 9)
Placebo vs ibuprofen 7% vs 25% 72% (49 to 85) 5 (4 to 10)

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated using simple proportions with data provided by author.


Most clinicians are aware of the discovery of 2 forms of cyclooxygenase (COX): COX-1, the constitutional form, produces prostaglandins involved in physiologic functions; COX-2, an inducible form, produces inflammatory prostaglandins. The distinction between the 2 forms led to a search for drugs that inhibit COX-2, sparing COX-1, in the expectation that such agents would be free of the serious GI toxicity caused by conventional (nonselective) NSAIDs. The first 2 COX inhibitors, celecoxib and rofecoxib, enjoyed successful launches in North America before any publications were available to assess their effectiveness and toxicity. In late 1999, 4 full reports, including these studies by Laine and Simon and their colleagues and 2 others by Langman and Emery (1, 2), were published; accompanying editorials raised doubts about the true value of these agents (3, 4). Overall, the 4 reports describe the experience of > 7000 patients with RA or OA treated for 6 to 52 weeks (Table).

Accepting that the COX-2 inhibitors are of similar efficacy to non-selective NSAIDs, the main clinical interest is in avoiding clinically important GI damage. During endoscopy, small and superficial ulcers that do not usually cause symptoms are frequently seen in the stomach and duodenum of patients taking conventional NSAIDs. The rates of these mainly nonclinical events with COX-2 inhibitors are approximately 25% of that with conventional NSAIDs. Physicians and patients are, however, more concerned with GI symptoms. Dyspepsia was reduced by only 2% to 3% with a COX-2 inhibitor. Although many patients have been studied in trials of COX-2 inhibitors, few instances of serious GI complications, such as bleeding or perforation, have occurred. The frequency of these potentially serious outcomes is approximately 1% with conventional NSAIDs; COX-2 inhibitors appear to provide a reduction of 0.5% to 1%. This means that 100 to 200 “typical” patients will have to be treated (NNT) with a COX-2 NSAID instead of a conventional NSAID to avoid 1 additional serious complication. In low-risk groups, the NNT for serious complications may be around 500 (4).

Many patients who are unable to tolerate several conventional NSAIDs will probably be switched to the newer agents, and some will benefit. Although not yet the topic of a published study, patients who are at high risk for serious GI complications (e.g., a history of ulcers or GI bleeding) and who need to take an NSAID will probably be the group for whom COX-2 inhibitors will be the most cost-effective. Considering the high cost of these new drugs and the widespread use of NSAIDs in most communities, the routine prescription of COX-2 inhibitors cannot be supported.

David Henry, MB, ChB
Patricia McGettigan, MD
University of Newcastle
Newcastle, New South Wales, Australia


1. Langman MJ, Jensen DM, Watson DJ, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA. 1999;282:1929-33.

2. Emery P, Zeidler H, Kvien TK, et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet. 1999;354:2106-11.

3. Beejay U, Wolfe MM. Cyclooxygenase 2 selective inhibitors: panacea or flash in the pan? Gastroenterology. 1999;117:1002-14.

4. Peterson WL, Cryer B. COX-1-sparing NSAIDs—is the enthusiasm justified? JAMA. 1999;282:1961-3.