Institute for Medical Technology Assessment, Erasmus University Rotterdam, PO Box 1738, 3000DR, Rotterdam, the Netherlands.
Center for Lysosomal and Metabolic Diseases, Department of Pediatrics Sophia's Children's Hospital, Rotterdam, the Netherlands.
Orphanet J Rare Dis. 2017 Dec 13;12(1):179. doi: 10.1186/s13023-017-0731-0.
Pompe disease is a rare, progressive, metabolic disease, and the first treatable inheritable muscle disorder. Enzyme replacement therapy (ERT) with alglucosidase alfa is disease specific and the only medicinal product authorized for the treatment of Pompe disease. Costs of ERT are very high as for most orphan drugs. This study investigates the cost-effectiveness of ERT compared to supportive treatment in adult patients with Pompe disease.
Survival probabilities were estimated from an international observational dataset (n = 283) using a time-dependent Cox model. Quality of life was estimated on a Dutch observational dataset using a previously developed conceptual model which links clinical factors to quality of life. Costs included costs of ERT, costs of drug administration and other healthcare costs. Cost-effectiveness was estimated using a patient-level simulation model (n = 90), synthesising the information from underlying models for survival, quality of life and costs. The cost-effectiveness model estimated the (difference in) lifetime effects and costs for both treatments. Two scenarios were modelled: (1) a worse case scenario with no extrapolation of the survival gain due to ERT beyond the observed period (i.e. from 10 years onwards); and (2) a best case scenario with lifetime extrapolation of the survival gain due to ERT. Effects were expressed in (quality adjusted) life years (QALYs). Costs were discounted at 4.0% and effects at 1.5%.
Substantial increases in survival were estimated - discounted incremental life years of ERT ranged from 1.9 years to 5.4 years in the scenarios without and with extrapolation of survival gains beyond the observed period. Quality of life was also significantly better for patients receiving ERT. Incremental costs were considerable and primarily consisted of the costs of ERT. Incremental costs per QALY were €3.2 million for scenario 1 and €1.8 million for scenario 2.
The availability of extended, prospectively collected, longitudinal observational data on the most important input parameters required to construct a cost-effectiveness model is quite exceptional for orphan diseases. The cost-effectiveness model showed substantial survival gains from ERT. Despite these substantial gains, ERT was not cost-effective in the treatment of adult Pompe disease because of the high cost of treatment.
庞贝病是一种罕见的、进行性的、代谢性疾病，也是第一种可治疗的遗传性肌肉疾病。阿糖苷酶 α 酶替代疗法（ERT）是一种针对疾病的特异性治疗方法，也是唯一获准治疗庞贝病的药物。由于大多数孤儿药的成本非常高，ERT 的成本也非常高。本研究调查了 ERT 与支持性治疗在成年庞贝病患者中的成本效益。
使用时间依赖性 Cox 模型，从国际观察性数据集（n=283）中估计生存概率。使用先前开发的概念模型，从荷兰观察性数据集估计生活质量，该模型将临床因素与生活质量联系起来。成本包括 ERT 的成本、药物管理成本和其他医疗保健成本。使用患者水平的仿真模型（n=90）估计成本效益，该模型综合了生存、生活质量和成本的基础模型中的信息。该成本效益模型估计了两种治疗方法的（差异）终生效果和成本。建模了两种情况：（1）一种最坏的情况，由于 ERT 观察期后（即 10 年以后）没有生存获益的外推；（2）一种最好的情况，ERT 的生存获益进行终生外推。效果以（质量调整）生命年（QALY）表示。成本和效果均以 4.0%贴现。
估计生存有了显著增加——在没有和有观察期后生存获益外推的情况下，ERT 的增量生命年分别为 1.9 年和 5.4 年。接受 ERT 的患者的生活质量也显著提高。增量成本相当大，主要由 ERT 成本组成。方案 1 的增量成本效益为每 QALY 320 万欧元，方案 2 的增量成本效益为每 QALY 180 万欧元。
对于孤儿病来说，能够获得构建成本效益模型所需的最重要输入参数的扩展、前瞻性、纵向观察数据是非常罕见的。成本效益模型显示 ERT 可显著提高生存率。尽管有这些显著的获益，但由于治疗费用高昂，ERT 在治疗成人庞贝病方面并不具有成本效益。
