Incidence of gastroduodenal ulcers in patients with rheumatoid arthritis after 12 weeks of rofecoxib, naproxen, or placebo: a multicentre, randomised, double blind study.
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 > or =3 mm. Gastric or duodenal ulcers > or =5 mm and erosions were also evaluated as secondary end points. Tolerability was assessed by adverse events.


RESULTS
The cumulative incidence of ulcers > or =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 > or =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.
Hawkey
C J
CJ
University Hospital, Nottingham, United Kingdom. cj.hawkey@nottingham.ac.uk
Laine
L
L
Simon
T
T
Quan
H
H
Shingo
S
S
Evans
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007783:Lactones / Q000009:adverse effects* / Q000627:therapeutic use; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects* / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000139:chemically induced*; D012307:Risk Factors; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen