Cost-effectiveness of Non-steroidal Anti-inflammatory Drugs Adjusting for Upper and Lower Gastrointestinal Toxicities in Rheumatoid Arthritis Patients

OBJECTIVE: This study was performed to assess the cost-effectiveness of cyclooxygenase-2 (COX2)-selective inhibitor, non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and non-selective NSAID with proton pump inhibitors (PPIs) while considering upper and lower gastrointestinal (GI) safety in patients with rheumatoid arthritis (RA). METHODS: A Markov model was used to estimate the costs and effectiveness. Estimates of therapeutic efficacy and upper/lower GI safety were based on results from large randomized controlled trials. The main outcome measure was cost effectiveness, based on the quality-adjusted life years (QALYs) gained. Safety parameters included clinical upper GI symptoms, uncomplicated ulcer, upper GI bleeding, upper GI perforation, clinical lower GI symptoms, lower GI bleeding, and lower GI perforation. Cost data were obtained from patients treated in a tertiary referral center in Korea. RESULTS: The expected three year cost was 3,052,800 Korean won (KRW) for COX2-selective inhibitor, 3,170,800 KRW for nonselective NSAID, and 3,325,900 KRW for non-selective NSAID with PPI. QALYs were 2.87446, 2.85320, and 2.85815, respectively. The total cost for COX2-selective inhibitor use was lower than non-selective NSAID, but QALY was higher, indicating that the incremental cost effectiveness ratio of COX2-selective inhibitor is superior. CONCLUSION: COX2-selective inhibitor has reasonable cost-effectiveness adjusted for upper and lower GI toxicity for patients with RA in Korea.

Cyclooxygenase-2 Inhibitors and Cardivascular Risk / 한양의대학술지

Serious concerns about the cardiovascular safety of rofecoxib had been present since the VIOXX(R) Gastrointestinal Outcomes Research (VIGOR) study first suggested that the drug may increase the risk of myocardial infarction. Subsequent data from major observational studies further implicated the association of rofecoxib with arterial thromboembolic disease. In September 2004, rofecoxib was withdrawn from the worldwide market based on the safety findings of the Adenomatous Polyp Prevention on VIOXX (APPROVe) study, which indicated an increase risk of myocardial infarction and stroke among subjects randomized to rofecoxib. In December 2004, the results of the Adenoma Prevention with Celecoxib (APC) study demonstrated a dose-related increase in the risk of cardiovascular events among patients randomized to celecoxib when compared with placebo. Two other large prospective prevention studies of celecoxib, the Prevention of Spontaneous Adenomatous Polyps (Pre SAP) trial and the Alzheimer's Disease Antiinflammatory Prevention Trial (ADAPT) did not show any sign of increased cardiovascular risk. None of the reported randomized trials studying any COX-2 selective imhibitor, thus far, has been specifically designed to examine cardiovascular outcomes. Hence, no cardiovascular hypotheses have yet been formally tested. Long-term and adequately powered prospective randomized clinical trials in relevant patient populations with clinically appropriate pre-specified cardiovascular end-points, ideally comparing COX-2 selective inhibitors with traditional NSAIDs, are required. Until these trials are completed, careful risk:benefit analysis of any putative increase in cardiovascular risk versus known gastrointestinal benefit for individual agents needs to be undertaken.