Cyclooxygenase-2 inhibitors: what went wrong?
Abstract
PURPOSE OF REVIEW: This review describes the biology underpinning the development of selective cyclooxygenase-2 inhibitors, documenting the clinical experience from the pivotal gastrointestinal safety trials to their eventual withdrawal or labelling with cardiovascular safety warnings.
RECENT FINDINGS: The elucidation of differences between the active sites of cyclooxygenase-1 and cyclooxygenase-2 allowed the targeted design of the selective cyclooxygenase-2 inhibitors known as coxibs. These were developed and marketed as non-steroidal anti-inflammatory drugs (NSAIDs) that had improved upper gastrointestinal safety compared with older non-selective NSAIDs. A large-scale study with arthritis patients to evaluate upper gastrointestinal safety, however, demonstrated that celecoxib was not superior in terms of upper gastrointestinal safety compared with the older non-selective NSAIDs that were used as comparators. In an equally large study with arthritis patients, a more selective cyclooxygenase-2 inhibitor, rofecoxib, did have improved upper gastrointestinal safety compared with the non-selective non-steroidal anti-inflammatory drug naproxen. Although concomitant clinical trial evidence emerged that rofecoxib increased cardiovascular risk, this was discounted by its pharmaceutical company owner. Despite the lack of improved upper gastrointestinal safety with celecoxib and the evidence of cardiovascular risk with rofecoxib, both agents had widespread clinical use for 4-5 years.…
Read the paper
Related studies
- Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial
- Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease
- Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience
- Celecoxib or naproxen treatment does not benefit depressive symptoms in persons aged 70 and over: findings from a randomized controlled trial
- Comparative Clinical Effectiveness of Nonsurgical Treatment Methods in Patients With Lumbar Spinal Stenosis: A Randomized Clinical Trial
- Efficacy and safety of adalimumab by intra-articular injection for moderate to severe knee osteoarthritis: An open-label randomized controlled trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.