酶替代疗法Fabry疾病:系统回顾可用的证据。

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Schaefer RM, Tylki-Szymanska Hilz乔丹

酶替代疗法Fabry疾病:系统回顾可用的证据。

药。2009年11月12日,69 (16):2179 - 205。doi: 10.2165 / 11318300-000000000-00000。

PubMed ID

19852524 (在PubMed

]

文摘

Fabry疾病是一种进步和危及生命的醣脂类存储障碍影响雄性和雌性。疾病的主要动力是糖脂的积累(globotriaosylceramide [GL-3])在不同的细胞类型,包括血管内皮细胞,肾细胞的类型,心肌细胞和神经元,这是由缺陷引起的溶酶体酶的活性,alpha-galactosidase。这种疾病通常在儿童或青少年时期。第一个表现反映外围的小神经纤维的参与和自主神经系统。随着年龄的增长,严重的并发症包括肾脏、心脏和大脑造成相当大的发病率和过早死亡。在美国以外,酶替代疗法(ERT) agalsidase阿尔法0.2毫克/公斤每隔一周(EOW)和agalsidaseβ1.0毫克/公斤EOW可供Fabry疾病患者的治疗,而agalsidaseβ1.0毫克/公斤EOW是唯一批准的药物在美国。分析的证据,系统回顾文献进行识别前瞻性随机化设计,对照试验(相关的)和非盲的功效研究agalsidase阿尔法和agalsidaseβ。MEDLINE和EMBASE数据库搜索;必威国际app入选标准的系统回顾前瞻性临床研究设计与量化评估ERT端点:双盲和开放的研究都是合格的。排除标准是评论文章、病例报告、案例研究、信件给编辑和文章基于注册表数据(Fabry结果调查或Fabry注册表)。 In addition, any studies with a retrospective design or data based on post hoc analyses were excluded. The evidence was reviewed with respect to the clinical benefits of ERT at the level of the end organ. A total of 9 RCTs and 23 open-label studies were identified for inclusion. The efficacy of ERT in Fabry disease has been measured against a variety of endpoints, the majority of which were subclinical parameters rather than clinical outcomes. Plasma levels of GL-3 together with accumulation in the kidney, heart and skin were the most commonly studied endpoints, followed by renal endpoints of proteinuria and glomerular filtration rate, whereas cardiac and neurological endpoints were not commonly studied. To date, only one RCT with ERT defined hard clinical outcomes in the form of cardiac, renal or cerebrovascular events, or death as its primary endpoint. The currently available data from prospective RCTs and open-label studies in patients with Fabry disease are more robust for ERT at a dose of 1 mg/kg EOW than a dose of 0.2 mg/kg EOW, although the beneficial effects of ERT with either dose or preparation are variable.

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药物靶点

药物	目标	类	生物	药理作用	行动
Agalsidase阿尔法	Globotriaosylceramide	集团	人类	未知的	代谢 配位体	细节
Agalsidaseβ	Globotriaosylceramide	集团	人类	是的	代谢 配位体	细节