An overview of economic evaluations for drugs used in rheumatoid arthritis - Focus on tumour necrosis factor-alpha antagonists

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 $US16 000 and $US20 000 per patient-year (2001 values), the potential greater efficacy of treatment with TNF alpha 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 TNF alpha 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 I year published incremental cost-effectiveness ratios (ICERs) of SUS34 800 per ACR 70% response criteria (ACR70) weighted response (duration 6 months, 1999 values) and $US96 166 (duration 1 year, 2002 values). Analyses that modelled costs and health outcomes beyond the first year reported ICER estimates ranging between $US26 800 (patients' lifetime, 1998 values) and $US40 308 (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 $US30 362 (10 years, 2002 values) to $US93 000 (22 years, 1998 values), and comparator costs ranged from $US22 593 (10 years, 2002 values) to $US84 000 (22 years, 1998 values).