Background The VIGOUR Study was a randomised, double-blind, clinical trial assessing the GI safety of rofecoxib 50 mg. once daily (n = 4047) versus naproxen 500 mg twice daily (n = 4029) in patients with rheumatoid arthritis. The mean age was 58 years; 80% of patients were female; 8% had a prior history of a GI ulcer or bleed; 82% reported NSAID use at baseline; 21% reported dyspepsia within 14 days prior to baseline; 56% took concomitant corticosteroids for their RA; the treatment groups were not different in these respects. The median duration of follow-up was 9.0 months, the maximum was 13 months.

Objectives To compare the rates of usage of gastroprotective agents (GPAs) and upper GI diagnostic procedures in patients treated with rofecoxib, a highly selective COX-2 inhibitor, compared to naproxen in the VIGOUR Study.

Methods We compared the treatment groups on their rates of new GPA usage (H2 receptor antagonists [H2RAs], proton pump inhibitors [PPIs], sucralfate, and prostaglandin analogues initiated after randomization), and investigator-initiated upper GI diagnostic radiologic and endoscopic procedures. Study participants were permitted to take OTC doses of H2RA’s; however, use of prescription GPA’s required discontinuation from the study. Use of upper GI diagnostic procedures was based on the investigators’ clinical judgment; there were no guidelines or restrictions on their use. Additional analyses were done in the subset of patients (n = 2937) reporting GI adverse experiences (AEs). 95% confidence intervals on rate ratios (RR) of rofecoxib to naproxen were calculated.

Results The incidence of confirmed intestinal perforations, ulcerations, and bleeds (PUBs), the primary endpoint in VIGOUR, was significantly lower with rofecoxib compared to naproxen (2.1% vs 4.5% per year; p < 0.001, relative risk 0.46). Patients treated with rofecoxib had lower rates of new GPA usage (11.2% vs 14.5%, RR = 0.77, CI: 0.68–0.87) than those treated with naproxen. Less use of H2RAs and PPIs occurred in the rofecoxib group than the naproxen group (H2RAs: 8.2% vs. 10.6%, RR = 0.77, CI: 0.67–0.89; PPIs: 3.8% vs. 5.6%, RR = 0.68, CI: 0.56–0.84). There were no significant differences between treatment groups in new prescriptions of prostaglandin analogues and sucralfate; few patients received these medications. Use of upper GI procedures was lower (4.3% vs. 5.9%, RR = 0.74, CI: 0.61–0.90) for patients treated with rofecoxib than for patients treated with naproxen. Among patients reporting GI AEs, those treated with rofecoxib required fewer new GPAs (25.5% vs. 32.2%, RR = 0.76, CI: 0.67–0.87) and upper GI procedures (11.5% vs. 14.7%, RR = 0.77, CI: 0.63–0.94) than did those treated with naproxen.

Conclusion In the VIGOUR Study, RA patients treated with the highly selective COX-2 inhibitor rofecoxib for up to 13 months had significantly fewer PUBs, required fewer new prescriptions for PPIs and H2RAs, and had fewer GI procedures than patients treated with naproxen.