The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders.
The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders.
复制标题
DOI：
10.3310/hta16390
复制
发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Logan, S
中科院分区：
文献类型：
--
作者：
Wyatt, K;Henley, W;Logan, S
目标：确定自然史，估计酶替代疗法（ERT）和底物替代疗法（SRT）对戈谢病，法布里病，粘多糖样病I型（MPS I），粘多糖样病II型（MPS II），庞贝氏症和尼曼匹克C型（NPC）diseases.DESIGN患者的有效性和成本：队列研究，包括前瞻性和回顾性的临床和患者报告的数据。使用广义线性混合模型估计年龄和性别校正的治疗效应。接受治疗的患者在治疗前和治疗期间提供数据。未治疗的患者提供了自然史数据。设置：英国国家专业委员会指定的溶酶体贮积症（LSD）治疗中心。参与者：诊断为戈谢病（n = 272）、法布里病（n = 499）、MPS I（n = 126）、MPS II（n = 58）、NPC（n = 58）或庞贝氏症（n = 93）谁参加了在英国的治疗中心。干预：ERT和SRT。主要结局指标：临床医生选择的临床结果，以反映疾病进展的每一个障碍;病人报告的生活质量（QoL）数据;治疗费用和病人报告的服务使用数据;住院人数，门诊和全科医生预约，药物使用，相关的家庭/照顾者的成本和QoL的影响有关的数据。在戈谢病患者（n = 175）中，ERT与血小板计数、血红蛋白、肝功能改善以及肝或脾肿大风险降低相关。ERT与QoL之间无相关性。在法布里病患者（n = 311）中，ERT治疗时间延长与左心室质量小幅下降和肾小球滤过率改善相关，但与卒中/短暂性脑缺血发作风险或助听器需求的变化无关。ERT使用持续时间与QoL和疲劳评分恶化之间存在统计学显著相关性。我们发现两种制剂（半乳糖苷酶β（Fabrazyme（），Genzyme）（n = 127）和半乳糖苷酶α（Replagal（），Shire HGT）（n = 91））之间的治疗有效性估计值无统计学差异，这两种制剂已获得许可用于这种疾病。在庞贝氏症（n = 77）中，我们的数据提供了一些证据，表明对成人发病患者的肌肉力量和活动性具有有益影响，通过6分钟步行测试进行测量;婴儿期庞贝氏症患者的数据不足以估计ERT之间的关联和结果。在MPS I受试者（n = 68）中，43例MPS I亚型Hurler病患者中有42例接受了骨髓移植。ERT与MPS I亚型Scheie病和硫酸乙酰肝素患者的任何结局指标之间均无显著相关性。ERT持续时间与儿童生长之间的相关性是MPS II患者（n = 39）中唯一具有统计学意义的发现。没有足够的数据为NPC疾病的患者得出任何关于SRT的有效性的结论。不同Erts的NHS当前年度成本意味着成人患者需要产生3.6至17.9个折扣质量调整生命年（Qs），儿童患者需要产生2.6至10.5个折扣Qs，每年接受Erts治疗才能被传统标准视为具有成本效益。结论：这些数据为ERT治疗LSD患者的有效性提供了进一步证据。然而，需要根据以下事实解释结果：数据是观察性的，并且由于MPS I、MPS II、庞贝氏症和NPC疾病患者数量较少而相对缺乏把握度。未来的工作应旨在有效地解决悬而未决的问题，这将需要一套共同的成果措施和他们的一致收集在所有treatment centers.FUNDING协议：这个项目是由NIHR卫生技术评估计划资助，并将在卫生技术评估;第16卷，第39号。更多项目信息见卫生技术评估方案网站。
OBJECTIVES: To determine natural history and estimate effectiveness and cost of enzyme replacement therapy (ERT) and substrate replacement therapy (SRT) for patients with Gaucher disease, Fabry disease, mucopolysaccharidosis type I (MPS I), mucopolysaccharidosis type II (MPS II), Pompe disease and Niemann-Pick type C (NPC) disease.DESIGN: Cohort study including prospective and retrospective clinical- and patient-reported data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data.SETTING: National Specialised Commissioning Group-designated lysosomal storage disorder (LSD) treatment centres in England.PARTICIPANTS: Consenting adults and children with a diagnosis of Gaucher disease (n = 272), Fabry disease (n = 499), MPS I (n = 126), MPS II (n = 58), NPC (n = 58) or Pompe disease (n = 93) who had attended a treatment centre in England.INTERVENTIONS: ERT and SRT.MAIN OUTCOME MEASURES: Clinical outcomes chosen by clinicians to reflect disease progression for each disorder; patient-reported quality-of-life (QoL) data; cost of treatment and patient-reported service-use data; numbers of hospitalisations, outpatient and general practitioner appointments; medication use; data pertaining to associated family/carer costs and QoL impacts.RESULTS: Seven hundred and eleven adults and children were recruited. In those with Gaucher disease (n = 175) ERT was associated with improved platelet count, haemoglobin, liver function and reduced risk of enlarged liver or spleen. No association was found between ERT and QoL. In patients with Fabry disease (n = 311) increased time on ERT was associated with small decreases in left ventricular mass and improved glomerular filtration rate, but not with changes in risk of stroke/transient ischaemic attacks or the need for a hearing aid. There was a statistically significant association between duration of ERT use and worsening QoL and fatigue scores. We found no statistical difference in estimates of treatment effectiveness between the two preparations, agalsidase beta (Fabrazyme(), Genzyme) (n = 127) and agalsidase alpha (Replagal(), Shire HGT) (n = 91), licensed for this condition. In Pompe disease (n = 77) our data provide some evidence of a beneficial effect on muscle strength and mobility as measured by a 6-minute walk test in adult-onset patients; there were insufficient data from infantile-onset Pompe patients to estimate associations between ERT and outcome. Among subjects with MPS I (n = 68), 42 of the 43 patients with MPS I subtype Hurler's disease had undergone a bone marrow transplant. No significant associations were found between ERT and any outcome measure for the MPS I subtype Scheie disease and heparan sulphate patients. An association between duration of ERT and growth in children was the only statistically significant finding among patients with MPS II (n = 39). There were insufficient data for patients with NPC disease to draw any conclusions regarding the effectiveness of SRT. The current annual cost to the NHS of the different ERTs means that between 3.6 and 17.9 discounted quality-adjusted life-years (QALYs) for adult patients and between 2.6 and 10.5 discounted QALYs for child patients would need to be generated for each year of being on treatment for ERTs to be considered cost-effective by conventional criteria.CONCLUSIONS: These data provide further evidence on the effectiveness of ERT in people with LSDs. However, the results need to be interpreted in light of the fact that the data are observational and the relative lack of power due to the small numbers of patients with MPS I, MPS II, Pompe disease and NPC disease. Future work should aim to effectively address the unanswered questions and this will require agreement on a common set of outcome measures and their consistent collection across all treatment centres.FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 39. See the HTA programme website for further project information.