Brennan M.R. Spiegel, MD; Laura Targownik, MD; Gareth S. Dulai, MD, MSHS; Ian M. Gralnek, MD, MSHS
Presented in part at the American Gastroenterological Association COX-2 Inhibitor Research Forum at Digestive Disease Week, May 2002, San Francisco, California.
Acknowledgments: The authors thank Emmett Keeler, PhD; Paul G. Shekelle, MD, PhD; Catherine MacLean, MD, PhD; Gerald Kominski, PhD; and A. Mark Fendrick, MD, for their thoughtful reviews of the manuscript.
Grant Support: Dr. Spiegel is supported by National Institutes of Health training grant DK-07180. Dr. Dulai is supported by National Institutes of Health K23 Career Development Award RR-16188. Dr. Gralnek is supported by a VA HSR&D Advanced Research Career Development Award.
Potential Financial Conflicts of Interest:Consultancies: I.M. Gralnek (Pharmacia); Honoraria: G.S. Dulai (Merck Pharmaceuticals), I.M. Gralnek (Merck Pharmaceuticals and Pharmacia); Grants received: I.M. Gralnek (Pharmacia).
Requests for Single Reprints: Ian M. Gralnek, MD, Veterans Administration Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, CURE Digestive Diseases Research Center, Center for the Study of Digestive Healthcare Quality and Outcomes, 11301 Wilshire Boulevard, Building 115, Room 215B, Los Angeles, CA 90073; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Spiegel, Targownik, Dulai, and Gralnek: Veterans Administration Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, CURE Digestive Diseases Research Center, Center for the Study of Digestive Healthcare Quality and Outcomes, 11301 Wilshire Boulevard, Building 115, Room 215B, Los Angeles, CA 90073.
Author Contributions: Conception and design: B.M.R. Spiegel, L. Targownik, I.M. Gralnek.
Analysis and interpretation of the data: B.M.R. Spiegel, L. Targownik, G.S. Dulai, I.M. Gralnek.
Drafting of the article: B.M.R. Spiegel, L. Targownik, G.S. Dulai, I.M. Gralnek.
Critical revision of the article for important intellectual content: B.M.R. Spiegel, L. Targownik, G.S. Dulai, I.M. Gralnek.
Final approval of the article: B.M.R. Spiegel, L. Targownik, G.S. Dulai, I.M. Gralnek.
Provision of study materials or patients: B.M.R. Spiegel, I.M. Gralnek.
Statistical expertise: B.M.R. Spiegel, L. Targownik, G.S. Dulai, I.M. Gralnek.
Obtaining of funding: I.M. Gralnek.
Administrative, technical, or logistic support: I.M. Gralnek.
Collection and assembly of data: B.M.R. Spiegel, I.M. Gralnek.
Rofecoxib and celecoxib (coxibs) effectively treat chronic arthritis pain and reduce ulcer complications by 50% compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). However, their absolute risk reduction is small and the cost-effectiveness of treatment is uncertain.
To determine whether the degree of risk reduction in gastrointestinal complications by coxibs offsets their increased cost compared with a generic nonselective NSAID.
Systematic review of MEDLINE and published abstracts.
Patients with osteoarthritis or rheumatoid arthritis who are not taking aspirin and who require long-term NSAID therapy for moderate to severe arthritis pain.
Naproxen, 500 mg twice daily, and coxib, once daily. Patients intolerant of naproxen were switched to a coxib.
Incremental cost per quality-adjusted life-year (QALY) gained.
Using a coxib instead of a nonselective NSAID in average-risk patients cost an incremental $275 809 per year to gain 1 additional QALY.
The incremental cost per QALY gained decreased to $55 803 when the analysis was limited to the subset of patients with a history of bleeding ulcers. The coxib strategy became dominant when the cost of coxibs was reduced by 90% of the current average wholesale price. In probabilistic sensitivity analysis, if a third-party payer was willing to pay $150 000 per QALY gained, then 4.3% of average-risk patients would fall within the budget.
The risk reduction seen with coxibs does not offset their increased costs compared with nonselective NSAIDs in the management of average-risk patients with chronic arthritis. However, coxibs may provide an acceptable incremental cost-effectiveness ratio in the subgroup of patients with a history of bleeding ulcers.
Relative to nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors have fewer gastrointestinal complications but cost more. The exact tradeoff between cost and effectiveness is unknown.
This analysis suggests that using rofecoxib and celecoxib rather than naproxen to treat chronic arthritis is cost-effective only for patients with a previous bleeding ulcer or if the cost of COX-2 inhibitors were 10% of its current average wholesale price.
At current prices, COX-2 inhibitors offer a cost-effective therapeutic option for treating chronic arthritis only for patients with a previous bleeding ulcer.
Truncated decision model.A
Table 1. Base-Case Clinical Probability Estimates
Meta-analysis using the fixed-effects model of randomized, controlled trials that report upper gastrointestinal dyspeptic symptoms in patients receiving a coxib versus a nonselective nonsteroidal anti-inflammatory drug.RR
Table 2. Ulcer Complication Rates (Including Symptomatic Ulcers, Ulcer Hemorrhages, and Ulcer Perforations) for Nonselective Nonsteroidal Anti-Inflammatory Drugs versus Coxibs as Reported in Published Randomized, Controlled Trials
Meta-analysis using the fixed-effects model of randomized, controlled trials that report clinically significant ulcer complications (symptomatic ulcer, ulcer hemorrhage, or ulcer perforation) in patients receiving a coxib versus a nonselective nonsteroidal anti-inflammatory drug.RR
Table 3. Cost Estimates
Table 4. Results of Cost-Utility Analysis under Varying Conditions
Table 5. Results of One-Way Sensitivity Analyses
Probabilistic sensitivity analysis using 1000 trials.QALYsolid line
Appendix Table 1. League Table of Incremental Cost per Quality-Adjusted Life-Year Values of Common Medical Interventions with Reference to Present Analysis
Appendix Table 2. Utilities, Duration, and Disutility for Modeled Health States
Appendix Table 3. League Table of Utility Values of Common Medical Conditions
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Spiegel BM, Targownik L, Dulai GS, Gralnek IM. The Cost-Effectiveness of Cyclooxygenase-2 Selective Inhibitors in the Management of Chronic Arthritis. Ann Intern Med. 2003;138:795-806. doi: 10.7326/0003-4819-138-10-200305200-00007
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Published: Ann Intern Med. 2003;138(10):795-806.
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