Rofecoxib and clinically significant upper and lower gastrointestinal events revisited based on documents from recent litigation.

INTRODUCTION: On the basis of published data, it is widely believed and cited that rofecoxib use is associated with approximately a 50% reduction in significant gastrointestinal (GI) complications such as bleeding.
METHODS: Data made available as part of litigation, including the Vioxx Gastrointestinal Outcomes Research trial and an Alzheimer's study, allow a reassessment of the reported benefits of rofecoxib in terms of a significant reduction in complicated GI events and in lower GI bleeding.
RESULTS: During the review process of the Vioxx Gastrointestinal Outcomes Research study, it was suggested that rofecoxib might have little benefit, with regard to GI toxicity, for patients with rheumatoid arthritis not treated with corticosteroids. Reanalysis of the original Merck data set showed 9 complicated confirmed events in the rofecoxib group compared with 10 in the naproxen group among corticosteroid nonusers and 7 versus 27 among corticosteroid users so that the difference between rofecoxib and naproxen in the occurrence of confirmed complicated perforations, ulcers or bleeds seemed to be entirely because of the effects within corticosteroid users. The claim that serious lower GI events were 54% lower with the use of the selective cyclooxygenase-2 inhibitor rofecoxib was stated to be based on an assessment blinded to treatment allocation. In fact, the choice did not represent the original blinded analysis that showed a nonsignificant difference, but rather was based on an assessment after treatment allocation was disclosed.
CONCLUSION: Examination and reanalysis of unpublished data regarding rofecoxib has failed to confirm a safety advantage of rofecoxib over traditional nonsteroidal anti-inflammatory drugs in terms of complicated upper or lower GI events.