NSAIDs: gastroprotection or selective COX-2 inhibitor?

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are effective adjuvant analgesics commonly encountered in palliative care. However, these drugs are associated with adverse effects that are primarily due to gastrointestinal toxicity, with resultant serious complications such as gastroduodenal perforations, ulcers and bleeds. This toxicity has been attributed to inhibition of cyclooxygenase-1 (COX-1). Factors known to increase this risk of toxicity include age above 65 years, classification of NSAID in terms of COX-1/COX-2 selectivity, previous history of complications and coadministration of aspirin, anticoagulants and corticosteroids. Selective inhibitors of cyclooxygenase-2 (COX-2) were developed in an attempt to reduce this association; trials to date confirm that these drugs do indeed have reduced incidence of gastroduodenal toxicity. Prior to the introduction of the COX-2 selective inhibitors, patients at high risk were often coprescribed a gastroprotective agent (such as misoprostol or a proton pump inhibitor) with a conventional NSAID. This review discusses the merits of both options and devises a treatment strategy for the safe and cost-effective use of these drugs in the palliative care population.

Have COX-2 inhibitors influenced the co-prescription of anti-ulcer drugs with NSAIDs?

AIMS: To quantify usage of COX-2 inhibitors compared with nonselective NSAIDs and to determine their impact (including financial) on the co-prescription of antipeptic ulcer (anti-PU) drugs. METHODS: The Irish General Medical Services prescription database (covering 1.2 million people) was examined for NSAID prescriptions during December 1999-November 2001. NSAID users were excluded during the first 6 months. During the next 12 months (study period) patients on NSAIDs (>or= 3 prescriptions) were identified. The study period and final 6 months provided data on co-prescription of anti-PU drugs. Age, gender, number of concomitant prescriptions, co-prescribing of anti-PU drugs and monthly cost were evaluated for 8 NSAIDs (n= 4 non-selective NSAIDs and n= 4 COX-2 inhibitors) and odds ratios (OR) calculated using logistic regression. RESULTS: COX-2 inhibitors were prescribed more frequently in older, female patients and those receiving multiple medications. After adjustment for age, gender and polypharmacy, anti-PU drugs were prescribed more frequently with COX-2 inhibitors (OR = 1.31 (1.23,1.40)). COX-2 inhibitors were up to 10-fold more expensive, median monthly costs (including anti-PU drugs) ranging from Euros 34.61 (COX-2 inhibitors) to Euros 3.26 (nonselective NSAIDs). CONCLUSIONS: Since COX-2 inhibitors are associated with increased rates of co-prescription of anti-PU drugs and are more expensive than non-selective NSAIDs, these results suggest that the expected cost-savings with COX-2 inhibitors may not be occurring in practice.

Potential effect of cyclooxygenase-2-specific inhibitors on the prevention of colorectal cancer: a cost-effectiveness analysis.

PURPOSE: To estimate the potential cost-effectiveness of colorectal cancer chemoprevention with cyclooxygenase-2-specific inhibitors (COX-2 inhibitors). METHODS: Using a decision analytic Markov model, we estimated the discounted cost per life-year saved for three strategies: a COX-2 inhibitor alone; as an adjunct to colonoscopy every 10 years in persons at average risk of colorectal cancer; and as an adjunct to colonoscopy every 5 years in persons with first-degree relatives who had colorectal cancer. RESULTS: In the base case, the incremental cost per life-year saved with a COX-2 inhibitor alone compared with no screening was 233,300 dollars in persons at average risk of colorectal cancer and 56,700 dollars in persons with 2 first-degree relatives who had the disease. Chemoprevention was both less effective and more costly than screening. The incremental cost per life-year saved with a COX-2 inhibitor as an adjunct to screening was 823,800 dollars in persons at average risk and 404,700 dollars in persons with 2 first-degree relatives who had colorectal cancer. Combining a COX-2 inhibitor with less frequent screening was not as cost-effective as screening at currently recommended intervals. Cost-effectiveness estimates were highly sensitive to the cost of COX-2 inhibitors and their effect on the risk of cancer. CONCLUSION: Chemoprevention of colorectal cancer with COX-2 inhibitors is likely to incur substantially higher costs per life-year saved than are currently recommended screening strategies. COX-2 inhibitor use as an adjunct to screening may increase life expectancy, although at prohibitive costs, and is unlikely to result in less frequent screening.

Pharmacoeconomics of coxib therapy.

The economic evaluation of health care programs is undertaken to assess health care costs and benefits. Part of the goal of cost-effectiveness analysis is to maximize health benefits given the constraint of limited health care resources. The identification of costs is critical in a cost-effectiveness analysis of clinical interventions. The recent introduction of the cyclooxygenase (COX)-2-selective inhibitors, coxibs, for treatment of rheumatoid arthritis, osteoarthritis, and acute pain gives rise to cost-effectiveness issues. These new agents provide similar efficacy with fewer gastrointestinal events compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), but are more expensive on a per-dose basis. However, several modeled cost analyses have suggested that COX-2 inhibitors are cost effective in subsets of patients because they are associated with fewer downstream costs, particularly medical and surgical treatment of gastrointestinal adverse effects. Three cost-effectiveness models of interventions for rheumatoid arthritis and osteoarthritis, including COX-2 inhibitors, are reviewed. Prospective clinical investigation of the potential costs and benefits of these new agents is necessary to further support these findings.