McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, Dickson R, Dundar Y, Greenhalgh J, Modell B, Olujohungbe A, Telfer P, Walley T
Liverpool Reviews and Implementation Group, University of Liverpool, UK.
Health Technol Assess. 2009 Jan;13(1):iii-iv, ix-xi, 1-121. doi: 10.3310/hta13010.
To assess the clinical effectiveness and cost-effectiveness of deferasirox for the treatment of iron overload associated with regular blood transfusions in patients with chronic anaemia such as beta-thalassaemia major (beta-TM) and sickle cell disease (SCD).
Electronic databases were searched up to March 2007.
Methods followed accepted procedures for conducting and reporting systematic reviews and economic evaluations.
A total of 14 randomised controlled trials (RCTs) involving a study population of 1480 (ranging from 13 to 586) met the inclusion criteria. There was a high degree of heterogeneity between trials in terms of trial design and outcome reporting. As such it was only possible to meta-analyse serum ferritin data from six trials making comparisons between deferiprone and DFO and combination therapy and DFO. Only one of the results was statistically significant, favouring combination therapy over DFO alone for serum ferritin at 12 months. How this translates into iron loading in organs such as the heart is unclear, nor was it possible to determine the long-term benefits of chelation therapy. Eight full economic evaluations (one full paper; seven abstracts) were included in the review. The results were generally consistent and appear to demonstrate the cost-effectiveness of deferasirox compared with DFO for the treatment of iron overload in a number of different patient populations and study locations. However, a number of assumptions and, in the case of the long-term studies, extrapolation from short-term RCT data were required, which render the results highly speculative at best. Because of the paucity of long-term data we developed a simple, short-term (1 year) model to assess the costs and benefits of deferasirox, deferiprone and DFO in patients with beta-TM and SCD from an NHS perspective. A number of assumptions were required to generate results and, as such, they should be interpreted as indicative rather than factual. Our model suggests that deferasirox may be a cost-effective strategy compared with DFO, at a cost per quality-adjusted life-year (QALY) below 30,000 pounds per year, for patients with beta-TM and SCD. However, this is highly dependent upon the age of the patient and the use and benefits of balloon infusers to administer DFO. Deferasirox compared with deferiprone is likely to be cost-effective only for young children. Furthermore, if deferiprone is proven to offer the same health benefits as deferasirox, the latter will not be cost-effective for any patient compared with deferiprone.
In the short term there is little clinical difference between any of the three chelators in terms of removing iron from the blood and liver. Deferasirox may be cost-effective compared with DFO in patients with beta-TM and SCD, but it is unlikely to be cost-effective compared with deferiprone. Elucidating the long-term benefits of chelation therapy, including issues of adverse events and adherence, should be the primary focus for future research. Future work should aim for consistency and transparency in reporting study design and results to aid decision-making when making comparisons across trials.
评估地拉罗司治疗慢性贫血患者（如重型β地中海贫血（β-TM）和镰状细胞病（SCD））因定期输血导致的铁过载的临床疗效和成本效益。
检索电子数据库至2007年3月。
采用公认的系统评价和经济评估的实施及报告程序。
共有14项随机对照试验（RCT）符合纳入标准，研究人群为1480例（范围从13至586例）。各试验在试验设计和结果报告方面存在高度异质性。因此，仅能对6项试验的血清铁蛋白数据进行荟萃分析，比较去铁酮与去铁胺以及联合治疗与去铁胺。仅有一项结果具有统计学意义，即12个月时联合治疗在血清铁蛋白方面优于单用去铁胺。这如何转化为心脏等器官的铁负荷尚不清楚，也无法确定螯合疗法的长期益处。该综述纳入了8项完整的经济评估（1篇全文；7篇摘要）。结果总体一致，似乎表明在地拉罗司与去铁胺治疗多种不同患者群体和研究地点的铁过载方面，地拉罗司具有成本效益。然而，需要一些假设，并且对于长期研究而言，需从短期RCT数据进行推断，这使得结果充其量具有高度推测性。由于长期数据匮乏，我们从英国国家医疗服务体系（NHS）的角度开发了一个简单的短期（1年）模型，以评估地拉罗司（DFX）、去铁酮（DFP）和去铁胺（DFO）对于β-TM和SCD患者的成本和效益。得出结果需要一些假设，因此，这些结果应被视为指示性而非实际性的。我们的模型表明，对于β-TM和SCD患者，与去铁胺相比，地拉罗司可能是一种具有成本效益的策略，每年每质量调整生命年（QALY）成本低于30,000英镑。然而，这高度依赖于患者年龄以及使用球囊注入器给予去铁胺的情况和益处。与去铁酮相比，地拉罗司可能仅对幼儿具有成本效益。此外，如果证明去铁酮与地拉罗司具有相同的健康益处，那么与去铁酮相比，地拉罗司对任何患者都不具有成本效益。
短期内，三种螯合剂在从血液和肝脏中去除铁方面临床差异不大。对于β-TM和SCD患者，与去铁胺相比，地拉罗司可能具有成本效益，但与去铁酮相比不太可能具有成本效益。阐明螯合疗法的长期益处，包括不良事件和依从性问题，应是未来研究的主要重点。未来的工作应旨在使研究设计和结果报告具有一致性和透明度，以有助于在跨试验比较时进行决策。
