Abstract
Background: HMG-CoA reductase inhibitors (statins) are potentially excellent candidate agents for patients with rheumatoid arthritis (RA). They reduce both cardiovascular risks and RA disease activity.
Objective: To evaluate the potential long-term effects of statin therapy among patients with RA, and to determine their associated cost effectiveness by incorporating both the cardiovascular and the anti-rheumatic benefits.
Methods: A Markov decision-analytic model was developed to simulate cardiovascular and RA disease profiles over time. The impact of statin therapy was estimated by adjusting the risk of coronary heart disease (CHD) events and changes in the RA Disease Activity Score (DAS28), based on the results of a randomized trial. The benefits (QALYs) and costs (in year 2005 values) were evaluated from a US payer perspective. A full uncertainty analysis, including a value-of-information (VOI) analysis, was undertaken to evaluate the importance of individual parameters.
Results: Using a 10-year time horizon, the additional cost and QALYs of statin therapy were estimated to be $US4690 and 0.44 QALYs, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of $US10 650 per QALY (95% CI 1525, 156 565). The QALY gain associated with statin therapy depended more on the anti-rheumatic effects of statin therapy than on its cardiovascular prevention effect. The VOI analysis found the long-term benefit of statin therapy (i.e. ≥12 months) and the consequent impact on quality of life to be the most uncertain and, therefore, influential parameters.
Conclusion: Our analysis indicates that the dual anti-inflammatory/cardiovascular benefits of statins could make this therapy highly cost effective in RA. However, uncertainties remain in the available data, warranting further research on refining the precise RA disease-activity benefits and health-utility changes associated with statin therapy, at least over a 12-month period.
Similar content being viewed by others
References
Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 2002; 46 (4): 862–73
Goodson N, Marks J, Lunt M, et al. Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s. Ann Rheum Dis 2005; 64 (11): 1595–601
Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 2003; 107 (9): 1303–7
Nagashima T, Okazaki H, Yudoh K, et al. Apoptosis of rheumatoid synovial cells by statins through the blocking of protein geranylgeranylation: a potential therapeutic approach to rheumatoid arthritis. Arthritis Rheum 2006; 54 (2): 579–86
Abeles AM, Pillinger MH. Statins as antiinflammatory and immunomodulatory agents: a future in rheumatologic therapy? Arthritis Rheum 2006; 54 (2): 393–407
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. Circulation 2002; 106 (25): 3143–421
Cziraky MJ, Willey VJ, McKenney JM, et al. Statin safety: an assessment using an administrative claims database. Am J Cardiol 2006; 97: 61C-8C
Palinski W, Napoli C. Unraveling pleiotropic effects of statins on plaque rupture. Arterioscler Thromb Vasc Biol 2002; 22: 1745–50
Sparrow CP, Burton CA, Hernandez M, et al. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscler Thromb Vasc Biol 2001; 21: 115–21
Youssef S, Stuve O, Patarroyo JC, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002; 420: 78–84
McCarey DW, McInnes IB, Madhok R, et al. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 2004; 363: 2015–21
The R project for statistical computing [online]. Available from URL: http://www.R-project.org [Accessed 2008 Nov 5]
Anderson KM, Odell PM, Wilson PW, et al. Cardiovascular disease risk profiles. Am Heart J 1991; 121: 293–8
D’Agostino RB, Russell MW, Huse DM, et al. Primary and subsequent coronary risk appraisal: new results from the Framingham study. Am Heart J 2000; 139: 272–81
Cook NR, Buring JE, Ridker PM. The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med 2006; 145(1): 21–9
Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333 (20): 1301–7
O’Hagan A. Research in elicitation. In: Upadhyay SK, Singh U, Dey DK, editors. Bayesian statistics and its applications. New Delhi: Anamaya Publishers, 2006: 375–82
Scott DL, Smith C, Kingsley G. Joint damage and disability in rheumatoid arthritis: an updated systematic review. Clin Exp Rheumatol 2003; 21 (5 Suppl. 31): S20–7
Reynolds RF, Obermeyer CM. Age at natural menopause in Spain and the United States: results from the DAMES project. Am J Hum Biol 2005; 17 (3): 331–40
Caspard H, Chan AK, Walker AM. Compliance with a statin treatment in a usual-care setting: retrospective database analysis over 3 years after treatment initiation in health maintenance organization enrollees with dyslipidemia. Clin Ther 2005; 27 (10): 1639–46
Meslop K, Boothroyd DB, Hlatky MA. Quality of life and time trade-off utility measures in patients with coronary artery disease. Am Heart J 2003; 145: 36–41
Goodacre S, Nicholl J, Dixon S, et al. Randomised controlled trial and economic evaluation of a chest pain observation unit compared with routine care. BMJ 2004; 328: 254
Ward S, Lloyd Jones M, Pandor A, et al. A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess 2007; 11 (14): 1–160, iii-iiv
Miller PS, Smith DG, Jones P. Cost effectiveness of rosuvastatin in treating patients to low-density lipoprotein cholesterol goals compared with atorvastatin, pravastatin, and simvastatin (a US analysis of the STELLAR trial). Am J Cardiol 2005; 95 (11): 1314–9
Michaud K, Messer J, Choi HK, et al. Direct medical costs and their predictors in patients with rheumatoid arthritis: a three-year study of 7527 patients. Arthritis Rheum 2003; 48(10): 2750–62
US Department of Health and Human Services, Agency for Healthcare Research and Quality, Health Cost and Utilization Project (HCUP). 2005 national and regional statistics on hospital stays from the NIS [online]. Available from URL: http://hcupnet.ahrq.gov [Accessed 2007 Aug 21]
Kobelt G, Eberhardt K, Geborek P. TNF inhibitors in the treatment of rheumatoid arthritis in clinical practice: costs and outcomes in a follow up study of patients with RA treated with etanercept or infliximab in southern Sweden. Ann Rheum Dis 2004; 63 (1): 4–10
Russell MW, Huse DM, Drowns S, et al. Direct medical costs of coronary artery disease in the United States. Am J Cardiol 1998; 81 (9): 1110–5
US Department of Labor, Bureau of Labor statistics. Consumer price index for medical care. Washington, DC: US Department of Labour [online]. Available from URL: http://www.bls.gov/cpi/home.htm [Accessed 2007 Aug 15]
Prevoo ML, van’t Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 44–8
Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update. Consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 2002; 106 (3): 388–91
van der Heijde DMFM, van’t Hof MA, van Riel PLCM, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a ‘disease activity score’. Ann Rheum Dis 1990; 49 (11): 916–20
Fries JF, Spitz PW, Kraines RG, et al. Measurement of patient outcome in arthritis. Arthitis Rheum 1980; 23(2): 137–45
Weintraub WS, Mahoney EM, Lamy A, CURE Study Investigators, et al. Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation. J Am Coll Cardiol 2005; 45 (6): 838–45
US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Life table for males and females. National vital statistics reports 2004 Nov 10; 53 (6) [online]. Available from URL: http://www.cdc.gov/nchs/data/nvsr/nvsr53/nvsr53_06.pdf [Accessed 2007 Aug 15]
US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Deaths, percentage of total deaths, and death rates for the 10 leading causes of death in selected age groups, by race and sex: United States, 2002—Con. National vital statistics Reports 2005 Mar 7; 53 (17) [online]. Available from URL: http://www.cdc.gov/nchs/data/nvsr/nvsr53_17.pdf [Accessed 2007 Aug 15]
Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 2005; 52 (2): 402–11
Briggs AH, Ades AE, Price MJ. Probabilistic sensitivity analysis for decision trees with multiple branches: use of the Dirichlet distribution in a Bayesian framework. Med Decis Making 2003; 23(4): 341–50
Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1999; 42 (2): 396
Ginnelly L, Claxton K, Sculpher MJ, et al. Using value of information analysis to inform publicly funded research priorities. Appl Health Econ Health Policy 2005; 4 (1): 37–46
Weinstein MC. From cost-effectiveness ratios to resource allocation: where to draw the line? In: Sloan FA, editor. Valuing health care: costs, benefits, and effectiveness of pharmaceuticals and other medical technologies. New York: Cambridge University Press, 1995: 77–97
Frolkis JP, Pearce GL, Nambi V. Statins do not meet expectations for lowering low-density lipoprotein cholesterol levels when used in clinical practice. Am J Med 2002; 113: 625–9
del Rincon I, Williams K, Stern MP, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001; 44: 2737–46
Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423 [online]. Available from URL: http://www.bmj.com/cgi/content/full/326/7404/1423 [Accessed 2008 Nov 19]
Grieve R, Hutton J, Green C. Selecting methods for the prediction of future events in cost-effectiveness models: a decision-framework and example from the cardiovascular field. Health Policy 2003; 64 (3): 311–24
Dessein PH, Joffe BI, Veller MG, et al. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J Rheumatol 2005; 32 (3): 435–42
Acknowledgements
No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.
Nick Bansback and Aslam Anis were involved in the study design, analysis and writing of the article. Roberta Ara and Sue Ward were involved in the CHD model design and writing of the article. Hyon Choi derived the study question, gave advice to the RA model and helped write the article. The authors thank Daphne Guh and Huiying Sun for their assistance in the development of the code and James Rankin for his editorial assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bansback, N., Ara, R., Ward, S. et al. Statin Therapy in Rheumatoid Arthritis. Pharmacoeconomics 27, 25–37 (2009). https://doi.org/10.2165/00019053-200927010-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00019053-200927010-00004