Rheumatoid Arthritis: Ara R

Bansback N, Ara R, Karnon J, Anis A. · Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital, Vancouver, British Columbia, Canada. · Pharmacoeconomics. · Pubmed #18429656 No free full text.

Abstract: We reviewed the clinical measures used in rheumatoid arthritis (RA) economic evaluations with respect to their relevance and sensitivity to changes in survival, health-related quality of life (HR-QOL) and costs. We compared the measures from the economic perspective and discussed the validity of methods used to extrapolate beyond the trial data. Cost-effectiveness evaluations of disease-modifying antirheumatic drugs in RA were identified by searching MEDLINE, EMBASE, Econlit and NHS EED databases. Studies were retained if they extrapolated beyond randomized controlled trial evidence using relationships between clinical measures, costs and utilities.In the 22 studies identified, clinical severity was measured using the Health Assessment Questionnaire (HAQ) Disability Index, the American College of Rheumatology (ACR) response criteria, the Disease Activity Score (DAS) or a combination of the HAQ and DAS. The HAQ is correlated with mortality, costs and HR-QOL instruments, and several studies used linear relationships to model these associations. However, a polynomial relationship or discrete states may be more appropriate for patients at the extremes of the disease spectrum, and numerous HAQ health states may be required to capture differences in mortality risk. While the ACR response criteria is a more comprehensive measure than the HAQ, it is a relative measure, which creates difficulties when estimating absolute changes in HR-QOL, costs and mortality risk. The evidence base linking DAS scores with HR-QOL instruments, costs and mortality is less robust, possibly due to the comparatively recent development of the measure and the limited number of possible scores (mild/moderate/severe). While there is some evidence of a relationship between DAS scores and costs, the DAS does not capture all aspects of HR-QOL, and no significant relationship has been established with mortality risk.Evidence suggests the HAQ to be the primary clinical measure for use in economic evaluations as it is measured in almost all clinical studies, and is closely correlated to health utilities, mortality and costs. While new developments suggest the sensitivity of health states may be improved by combining the HAQ with measures such as the DAS, further research is required in this area. Further research is also required to explore the advantages in using either continuous or discrete health states.

Bansback NJ, Regier DA, Ara R, Brennan A, Shojania K, Esdaile JM, Anis AH, Marra CA. · Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK. · Drugs. · Pubmed #15733011 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease that affects approximately 0.5-1% of the adult population. The introduction of new disease-modifying antirheumatic drugs (DMARDs) such as leflunomide, anakinra and the tumour necrosis factor (TNF)-alpha antagonists (infliximab, etanercept and adalimumab) have transformed the management of RA. In particular, the last class of agents has generated substantial controversy. Costing between 16,000 US dollars and 20,000 US dollars per patient-year (2001 values), the potential greater efficacy of treatment with TNFalpha antagonists comes at much higher drug costs, making these agents natural candidates for cost-effectiveness analyses (CEAs).A MEDLINE search (until 31 January 2004) identified six original CEAs evaluating TNFalpha antagonists in RA. The aim of a CEA is to facilitate the allocation of scarce health resources and to inform policy decisions. However, to enhance the reliability and relevance of these analyses to policy makers, there must be similarity between the methodologies used. Recently, the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) group produced a document to define such a reference case; the OMERACT document was used as a foundation to structure comparisons and highlight discrepancies.The methodologies employed in each analysis differed; in particular, disparate time horizons, comparators, quantities of drug and treatment sequences prohibit the comparison of cost effectiveness between studies. Outcomes also differed between the analyses. Most reported health-related quality of life (HR-QOL) in quality-adjusted life-years (QALYs). The QALYs metric was based on preference scores that were typically derived from linear regressions using the Health Assessment Questionnaire (HAQ). However, models also used American College of Rheumatology (ACR) criteria, as well as the disease activity score (DAS). Common to all studies was the lack of data from long-term randomised studies where efficacy and resource consumption in comparison with standard care has been investigated. As such, investigators combined short-term randomised control trial data with that of a long-term observational cohort, and modelled cost effectiveness over an appropriate time horizon. In addition, most analyses lacked rigorous sensitivity analysis to examine the impact of uncertainty in the parameters.Those analyses that examined time horizons of 6 months and 1 year published incremental cost-effectiveness ratios (ICERs) of 34,800 US dollars per ACR 70% response criteria (ACR70) weighted response (duration 6 months, 1999 values) and 96,166 US dollars (duration 1 year, 2002 values). Analyses that modelled costs and health outcomes beyond the first year reported ICER estimates ranging between 26,800 US dollars (patients' lifetime, 1998 values) and 40,308 US dollars (10 years, 2002 values). In terms of HR-QOL, the analyses reported incremental QALYs that ranged from 0.116 (over 19 years) to 1.6 (over 10 years). Discounted costs of therapy ranged from 30,362 US dollars (10 years, 2002 values) to 93,000 US dollars (22 years, 1998 values), and comparator costs ranged from 22,593 US dollars (10 years, 2002 values) to 84,000 US dollars (22 years, 1998 values).

Bansback N, Ara R, Ward S, Anis A, Choi HK. · Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital, Vancouver, British Columbia, Canada. · Pharmacoeconomics. · Pubmed #19178122 No free full text.

Abstract: 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. 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. 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. Using a 10-year time horizon, the additional cost and QALYs of statin therapy were estimated to be USD4690 and 0.44 QALYs, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of USD10 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. >or=12 months) and the consequent impact on quality of life to be the most uncertain and, therefore, influential parameters. 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.