Incidence of gastroduodenal ulcers in patients with rheumatoid arthritis after 12 weeks of rofecoxib, naproxen, or placebo: a multicentre, randomised, double blind study
- C J Hawkey1,
- L Laine2,
- T Simon3,
- H Quan3,
- S Shingo3,
- J Evans3,
- on behalf of the Rofecoxib Rheumatoid Arthritis Endoscopy Study Group
- 1University Hospital, Nottingham, United Kingdom
- 2USC School of Medicine, Los Angeles, CA, USA
- 3Merck Research Laboratories, West Point, PA, USA
- Correspondence to:
Professor C J Hawkey, School of Medical and Surgical Sciences, Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, UK;
- Accepted 17 December 2002
Background: Previous studies in patients with osteoarthritis have suggested that the selective cyclooxygenase (COX)-2 inhibitor rofecoxib results in less gastrointestinal damage than non-selective non-steroidal antiinflammatory drugs (NSAIDs). This study compared the incidence of endoscopically detected gastroduodenal ulcers in rheumatoid arthritis patients treated with rofecoxib or a non-selective NSAID.
Methods: In this multicentre, randomised, double blind, 12 week study, patients with rheumatoid arthritis were allocated to rofecoxib 50 mg once daily (n=219), naproxen 500 mg twice daily (n=220), or placebo (n=221). Endoscopy was performed at baseline and at six and 12 weeks. Lifetable analysis and log rank tests were used to analyse the incidence of gastroduodenal ulcers ≥3 mm. Gastric or duodenal ulcers ≥5 mm and erosions were also evaluated as secondary end points. Tolerability was assessed by adverse events.
Results: The cumulative incidence of ulcers ≥3 mm at 12 weeks was significantly higher in patients on naproxen (25.5%) than in patients receiving rofecoxib (6.8%; difference 18.7% (95% confidence interval (CI) 11.7%, 25.7%); p<0.001) or placebo (2.9%; difference 22.6% (95% CI 16.1%, 29.1%); p<0.001). The difference between rofecoxib (6.8%) and placebo (2.9%) did not reach statistical significance (p=0.066). Results were similar for ulcers ≥5 mm and for mean changes from baseline in the number of gastroduodenal erosions. The overall incidence of clinical adverse events was similar among treatment groups (61% of patients on placebo, 62% in patients on rofecoxib, and 66% in patients on naproxen).
Conclusions: Rofecoxib 50 mg daily (twice the dose recommended for this patient population) resulted in a lower incidence of endoscopically detected gastroduodenal ulcers and erosions than treatment with naproxen 500 mg twice daily.
- cyclooxygenase-2 inhibitor
- rheumatoid arthritis
- gastrointestinal tolerability
- non-steroidal anti-inflammatory drugs
- COX, cyclooxygenase
- NSAIDs, non-steroidal anti-inflammatory drugs
- OA, osteoarthritis
- PUBs, gastrointestinal perforations, ulcers, or bleeding episodes
- RA, rheumatoid arthritis