|
Cost-effectiveness analysis of rituximab treatment in patients in Germany with rheumatoid arthritis after etanercept-failure |
Merkesdal S, Kirchhoff T, Wolka D, Ladinek G, Kielhorn A, Rubbert-Roth A |
|
|
Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CRD summary This study assessed the cost-effectiveness of rituximab compared with a second anti-tumour necrosis factor-alpha treatment, as second-line biological treatment for patients with active rheumatoid arthritis and an inadequate response to first-line etanercept. The authors concluded that rituximab was cost-effective from the perspective of the health care payer, especially when considering productivity losses. The cost-effectiveness framework was conventional and methodologically sound and the authors’ conclusions appear to be valid. Type of economic evaluation Study objective This study assessed the cost-effectiveness of rituximab compared with a second anti-tumour necrosis factor (TNF)-alpha treatment, as the second-line biological treatment for patients with active rheumatoid arthritis and an inadequate response to first-line etanercept. Interventions The standard treatment consisted of adalimumab in combination with methotrexate, followed by infliximab in combination with methotrexate, then gold preparations, then cyclosporin A, and lastly supportive therapy of only methotrexate. Adalimumab was given subcutaneously at 40mg every other week and infliximab was given at 3mg per kg on weeks zero, two, and six, and then every eight weeks. Rituximab treatment was given with methotrexate, and this was followed by the standard treatment sequence. Rituximab treatment consisted of two doses of 1mg intravenously, plus 100mg of methylprednisolone intravenously on day one, every nine months. Methods Analytical approach:The analysis was based on a Markov model, with a lifetime horizon. The authors stated that the perspective of the health care payer was adopted.
Effectiveness data:A literature review was undertaken to identify those relevant randomised controlled trials (RCTs) that satisfied inclusion criteria for outcome measure, patient population, and comparators. The Randomized Evaluation of Long-Term Efficacy of Rituximab (REFLEX) trial was used for rituximab. Weighted averages of the American College of Rheumatology (ACR) response categories 20, 50, and 70 were calculated, and these were the key endpoints of the trials. An adjustment was made using placebo (methotrexate) as a common comparator. The ACR response categories were converted into Health Assessment Questionnaire (HAQ) scores using data from the REFLEX trial. Mortality data were based on German life tables.
Monetary benefit and utility valuations:The utility values were estimated by converting HAQ scores into health utility states, using a standardised formula, based on published cost-effectiveness models for rheumatoid arthritis.
Measure of benefit:Quality-adjusted life-years (QALYs) were the summary benefit measure and they were discounted at an annual rate of 3.5%.
Cost data:The economic analysis included the following cost categories: drugs (acquisition, administration, and monitoring), out-patient and in-patient care, and productivity losses due to rheumatoid arthritis. Drug monitoring included physician visits and laboratory tests. Drug administration consisted of the time used by the respective health care personnel. Patterns of resource consumption were based on label dosages for drugs. Drug costs were based on German retail prices to pharmacists. In-patient treatment was related to the decline in physical function (HAQ score) and in-patient costs were from the German Collaborative Arthritis Centres. The indirect cost of impaired work capacity due to rheumatoid arthritis was also based on HAQ score and data from the German Collaborative Arthritis Centres. All costs were in Euros (EUR) and an annual discount rate of 3.5% was applied. The price year was 2008.
Analysis of uncertainty:One-way sensitivity analyses were undertaken to evaluate the uncertainty around the key parameters. Either published or arbitrary ranges of values were used. The response rates, average time on treatment, and patterns of resource use were further tested in a probabilistic analysis, based on Monte Carlo simulation. Results Compared with standard therapy, rituximab increased the costs by EUR 13,922 and led to a gain of 0.57 QALYs, resulting in an incremental cost per QALY gained of EUR 24,517 (EUR 15,565 when including indirect costs). This was below the commonly cited threshold of EUR 50,000 per QALY.
The most influential inputs were the assumptions for rituximab dosage (every six months instead of every nine months), HAQ score deterioration with treatment, HAQ score benefits, and the discount rate. In all cases the incremental cost per QALY with rituximab remained below EUR 50,000.
The probability of rituximab having a cost-utility ratio below the threshold of EUR 30,000 was 77% and below EUR 50,000 it was 90%. Authors' conclusions The authors concluded that rituximab was cost-effective from the perspective of the health care payer, especially when productivity losses were considered. CRD commentary Interventions:The authors stated that the comparators were selected on the basis of expert opinion in Germany. This might not reflect the treatment patterns in other health care settings, but standard biological agents were considered.
Effectiveness/benefits:A systematic review of the literature was appropriately carried out to identify the relevant sources of data. The authors provided the key inclusion criteria, which should ensure the identification of valid evidence. Indirect comparison data was used, with methotrexate or placebo as the common comparator, due to a lack of direct head-to-head trial data. The method used to combine the data from different sources was described and appears to have been appropriate, but these sources were not described. The method used to derive the utility values was described and a standard tool for patients with rheumatoid arthritis was used. QALYs were a valid benefit measure given the impact of arthritis on quality of life.
Costs:The economic analysis included those cost categories relevant to the stated perspective. A broader perspective that included productivity losses was also considered. The costs were presented as category totals and were not broken down in individual items. The data sources were reported for most categories and the patterns of resource use were varied in the sensitivity analysis. A key cost item was the frequency of administration of rituximab (every six versus nine months) and its impact on the results was investigated in the sensitivity analysis. The price year was reported, which will allow reflation exercises for other time periods.
Analysis and results:The results were clearly reported and a valid incremental approach was used to synthesise the costs and benefits of the two strategies. The uncertainty was satisfactorily investigated, using various approaches that considered different aspects of parameter uncertainty. Conventional discounting was applied to both the costs and the benefits. The authors compared their results with those of other published economic evaluations of rituximab and these were generally similar. Future studies should compare rituximab as a second-line option after the first-line failure of the anti-TNF abatacept.
Concluding remarks:The cost-effectiveness framework was conventional and methodologically sound and the authors’ conclusions appear to be valid. Funding Supported by Roche Pharma AG, Germany, and F. Hoffman-La Roche Ltd, Switzerland. Bibliographic details Merkesdal S, Kirchhoff T, Wolka D, Ladinek G, Kielhorn A, Rubbert-Roth A. Cost-effectiveness analysis of rituximab treatment in patients in Germany with rheumatoid arthritis after etanercept-failure. European Journal of Health Economics 2010; 11(1): 95-104 Indexing Status Subject indexing assigned by NLM MeSH Aged; Antibodies, Monoclonal, Murine-Derived /economics /therapeutic use; Antirheumatic Agents /economics /therapeutic use; Arthritis, Rheumatoid /drug therapy /economics; Cost-Benefit Analysis; Etanercept; Female; Germany; Humans; Immunoglobulin G /economics /therapeutic use; Immunosuppressive Agents /economics /therapeutic use; Male; Markov Chains; Middle Aged; Models, Econometric; Probability; Quality-Adjusted Life Years; Receptors, Tumor Necrosis Factor /therapeutic use; Rituximab; Surveys and Questionnaires; Treatment Failure AccessionNumber 22010000721 Date bibliographic record published 12/01/2011 Date abstract record published 19/01/2011 |
|
|
|