BACKGROUND: Celecoxib and rofecoxib have been used in Norway since 2000. These cyclooxygenase 2 inhibitors (COX-2 inhibitors) have no better clinical efficacy than older non-steroid anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis or osteoarthritis, but may possibly lead to a lower incidence of upper gastrointestinal ulcers. MATERIAL AND METHODS: Published and unpublished clinical data on side effects were examined and interpreted. The aim was to evaluate the general safety of these new drugs compared with older NSAIDs. RESULTS: The incidence of side effects is addressed in two large published studies comparing COX-2 inhibitors with other NSAIDs. Only rofecoxib showed an unequivocal lower incidence of complicated upper gastrointestinal ulcers. However, the incidence of serious side effects was significantly higher in the rofecoxib group. In the other study there was a trend towards more serious side effects in the celecoxib group. INTERPRETATION: The available clinical data do not suggest that COX-2 inhibitors are safer drugs than other NSAIDs.
Population rates of upper gastrointestinal (GI) hemorrhage have been observed to increase with the introduction and rapid uptake of selective cyclooxygenase-2 (COX-2) inhibitors. Changes in COX-2 inhibitor use and upper GI bleeding rates in regions with relatively restrictive drug policies (e.g., British Columbia) have not been compared with changes in regions with relatively less restrictive drug policies (e.g., Ontario).
We collected administrative data for about 1.4 million people aged 66 years and older in British Columbia and Ontario for the period January 1996 to November 2002. We examined temporal changes in the prevalence of NSAID use and admissions to hospital because of upper GI hemorrhage in both provinces using cross-sectional time series analysis.
During the period studied, the prevalence of NSAID use in British Columbia's population of older people increased by 25% (from 8.7% to 10.9%; p
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To evaluate the cost effectiveness of the cyclooxygenase 2 (COX-2) selective nonsteroidal antiinflammatory drug (NSAID) rofecoxib compared with naproxen and the COX-2 NSAID celecoxib compared with ibuprofen and diclofenac.
Cost-effectiveness analysis based on a 5-year Markov model. Probability estimates were derived from detailed data of 2 randomized trials and a systematic search of the medical literature. Utility estimates were obtained from 60 randomly selected members of the general public. Cost estimates were obtained from Canadian provincial databases. Incremental cost-effectiveness ratios were calculated for patients at average risk of upper gastrointestinal (UGI) events and for high-risk patients with a prior history of a UGI event. Subjects were patients with osteoarthritis or rheumatoid arthritis (RA) where a decision has been made to treat with NSAIDs but who do not require low-dose aspirin. Main outcome measures were proportion of patients with clinical or complicated UGI events, quality-adjusted life expectancy, and life expectancy.
Evaluation of rofecoxib versus naproxen in patients with RA at average risk resulted in costs per quality-adjusted life year (QALY) gained of $Can271,188. Celecoxib was dominated by diclofenac in average-risk patients. Both rofecoxib and celecoxib are cost-effective in high-risk patients. Analyses by age groups and assuming a threshold of Can$50,000 per QALY gained, suggest that rofecoxib or celecoxib would be cost-effective in patients aged over 76 and 81, respectively, without additional risk factors.
Both rofecoxib and celecoxib are economically attractive in high risk and elderly patients. They are not economically attractive in patients at average risk. Coprescription of proton-pump inhibitors with COX-2 NSAIDs is not economically attractive for patients at high risk.
Cyclooxygenase-2 (COX-2) inhibitors belong to a new class of drugs which have anti-inflammatory efficacy similar to that of traditional non-steroidal anti-inflammatory drugs (NSAIDs), but are associated with a reduced incidence of adverse upper gastrointestinal events. Biochemical evidence that COX-2 inhibitors could promote or exacerbate a tendency to thrombosis is supported by recent results from clinical trials and case reports. Two agents in this class, celecoxib and rofecoxib, have been listed on the Pharmaceutical Benefits Scheme (PBS) for very broad indications in chronic arthropathies, suggesting that they will move into widespread community use. It is important to canvass the possibility that use of these agents could be associated with thrombotic events.
Comment In: Med J Aust. 2002 Jan 21;176(2):88-9; author reply 8911936297
Rheumatoid arthritis and osteoarthritis are prevalent and costly conditions. A large proportion of the direct costs associated with these conditions relates to management of iatrogenic side effects. The cyclooxygenase (COX)-2-specific inhibitors lead to equivalent control of pain and disability compared with traditional NSAIDs. However, the COX-2-specific inhibitors have significant potential to reduce health-care costs, principally through the reduction of side effects. These cost savings are most likely to be realized through reductions in costs associated with dyspepsia and upper gastrointestinal ulcers and bleeding. Reduced indirect costs through improved disability scores and improved health-related quality of life are also predictable with the use of COX-2-specific inhibitors. This is accomplished without the attendant increase in risk to the gastrointestinal tract associated with traditional NSAIDs.
Recent debate has emerged regarding the cardiovascular safety of selective cyclooxygenase 2 inhibitors and the possible cardioprotective effect of naproxen sodium. We compared the rates of acute myocardial infarction (AMI) among elderly patients dispensed selective cyclooxygenase 2 inhibitors, naproxen, and nonselective nonnaproxen nonsteroidal anti-inflammatory drugs (NSAIDs).
We conducted a population-based retrospective cohort study using administrative health care data from Ontario, Canada, from April 1, 1998, to March 31, 2001. We identified NSAID-naive cohorts of subjects aged 66 years and older in whom treatment was initiated with celecoxib (n = 15 271), rofecoxib (n = 12 156), naproxen (n = 5669), and nonnaproxen nonselective NSAIDs (n = 33 868), along with a randomly selected control cohort not exposed to NSAIDs (n = 100 000). Multivariate Cox proportional hazards models were used to compare AMI rates between study drug groups while controlling for potential confounders.
Relative to control subjects, the multivariate model showed no significant differences in AMI risk for new users of celecoxib (adjusted rate ratio [aRR], 0.9; 95% confidence interval [CI], 0.7-1.2), rofecoxib (aRR, 1.0; 95% CI, 0.8-1.4), naproxen (aRR, 1.0; 95% CI, 0.6-1.7), or nonnaproxen nonselective NSAIDs (aRR, 1.2; 95% CI, 0.9-1.4).
The findings of this observational study suggest no increase in the short-term risk of AMI among users of selective cyclooxygenase 2 inhibitors as commonly used in clinical practice. Furthermore, the findings do not support a short-term reduced risk of AMI with naproxen.