Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs?BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7349.1287 (Published 01 June 2002) Cite this as: BMJ 2002;324:1287
Adequate analysis of the CLASS trial indicates that this may not be the case
- Peter Jüni, senior research fellow (firstname.lastname@example.org),
- Anne WS Rutjes, research fellow,
- Paul A Dieppe, professor of health services research
- Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, Netherlands
- Departments of Rheumatology, and Social and Preventive Medicine, University of Berne, 3010 Berne, Switzerland
- MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol BS8 2PR
Selective cyclo-oxygenase 2 (COX 2) inhibitors, including celecoxib (Celebrex) and rofecoxib (Vioxx), are hypothesised to have a lower risk of gastrointestinal complications than traditional non-steroidal anti-inflammatory drugs.1 In September 2000 the celecoxib long term arthritis safety study, better known as CLASS, was published in JAMA.2 This trial, widely cited and distributed, concluded that a COX 2 inhibitor was associated with a lower incidence of complications than traditional non-steroidal anti-inflammatory drugs. What was much less widely publicised were criticisms that contradicted this conclusion.
CLASS was reported as a three arm trial comparing celecoxib 800 mg/day with ibuprofen 2400 mg/day and diclofenac 150 mg/day in osteoarthritis or rheumatoid arthritis. Clinically relevant upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction) and symptomatic ulcers during the first six months of treatment were described as the two main outcome measures, comparing incidence rates for celecoxib and a traditional non-steroidal anti-inflammatory drug (fig 1). It was concluded that, compared with the traditional non-steroidal anti-inflammatory drug, celecoxib “was associated with a lower incidence of symptomatic ulcers and ulcer complications combined.”3 The trial was funded by celecoxib's manufacturer Pharmacia.
An article in the Washington Post in August 20013 and two letters published in JAMA in November 2001 4 5 drew attention to the fact that complete information available to the United States Food and Drug Administration contradicted these conclusions. The paper reporting CLASS2 actually referred to the combined analysis of the results …