Henry Nathaniel, Jovanović Jelena, Schlueter Max, Kritikou Persefoni, Wilson Koo, Myrén Karl-Johan
a IQVIA , London , UK.
b Swedish Orphan Biovitrum AB , Stockholm , Sweden.
J Med Econ. 2018 Apr;21(4):318-325. doi: 10.1080/13696998.2017.1405816. Epub 2017 Dec 4.
Prophylaxis with recombinant factor VIII (rFVIII) is the standard of care for severe hemophilia A in Sweden. The need for frequent injections with existing rFVIII products may, however, result in poor adherence to prophylaxis, leading to increased bleeding and long-term joint damage. Recombinant FVIIIFc (rFVIIIFc) is an extended half-life fusion protein which can offer prolonged protection and reduced dosing frequency. The objective of this study was to evaluate the cost-utility of prophylaxis with rFVIIIFc in severe hemophilia A from the perspective of the Swedish health system.
A Markov model was built to estimate lifetime costs and benefits of prophylaxis with rFVIIIFc vs rFVIII products. Clinical outcomes were represented by annualized bleeding rate (ABR) and quality of life via disutility applied to bleeding events and injection frequency. Costs included the cost of FVIII for routine prophylaxis and bleed resolution. The pooled comparator was costed by weighting the cost of individual products by their market share.
In the base case, rFVIIIFc was dominant vs the pooled comparator. Savings of SEK 9.0 million per patient resulted from lower factor consumption for prophylaxis and bleed resolution. Fewer bleeds and reduced injection frequency yielded an estimated 0.59 quality-adjusted life years (QALYs). Results were sensitive to drug dosage and robust to variation in other parameters. Probabilistic sensitivity analysis suggested a greater than 85% probability of rFVIIIFc being cost-effective at a willingness-to-pay threshold of 500,000 SEK/QALY.
Due to unavailibilty of patient-level data, treatment benefit was based on a non-adjusted indirect comparison. Dosing and treatment outcomes were assumed to persist over the model duration in the absence of long-term outcome data.
The results suggest that rFVIIIFc may be a cost-effective option for hemophilia A prophylaxis, generating greater quality of life and reduced costs for the Swedish payer compared to more frequently administered rFVIII alternatives.
在瑞典，使用重组凝血因子VIII（rFVIII）进行预防是重度A型血友病的标准治疗方法。然而，由于需要频繁注射现有的rFVIII产品，可能导致预防依从性差，进而增加出血风险和长期关节损伤。重组凝血因子VIII-融合蛋白（rFVIIIFc）是一种半衰期延长的融合蛋白，可提供更长时间的保护并减少给药频率。本研究的目的是从瑞典卫生系统的角度评估rFVIIIFc用于重度A型血友病预防的成本效益。
构建马尔可夫模型以估计使用rFVIIIFc与rFVIII产品进行预防的终身成本和效益。临床结局通过年化出血率（ABR）以及应用于出血事件和注射频率的失用率来体现生活质量。成本包括常规预防和解决出血所需的凝血因子VIII成本。通过按市场份额对单个产品成本进行加权来计算合并对照的成本。
在基础案例中，rFVIIIFc相对于合并对照具有优势。由于预防和解决出血所需的凝血因子消耗较低，每位患者节省了900万瑞典克朗。出血减少和注射频率降低产生了约0.59个质量调整生命年（QALY）。结果对药物剂量敏感，对其他参数的变化具有稳健性。概率敏感性分析表明，在支付意愿阈值为500,000瑞典克朗/QALY时，rFVIIIFc具有成本效益的概率大于85%。
由于缺乏患者层面的数据，治疗效益基于未经调整的间接比较。在没有长期结局数据的情况下，假设剂量和治疗结局在模型持续时间内持续存在。
结果表明，与更频繁给药的rFVIII替代方案相比，rFVIIIFc可能是A型血友病预防的一种具有成本效益的选择，可为瑞典付款人带来更高的生活质量并降低成本。
