Pharmacy Department, Hospital Universitario Marques de Valdecilla, Santander, Spain
Neurology Department, Hospital Universitario Marques de Valdecilla, Santander, Spain.
Eur J Hosp Pharm. 2020 Jul;27(4):194-201. doi: 10.1136/ejhpharm-2018-001823. Epub 2019 Mar 19.
To carry out a systematic review of the literature to analyse the efficacy and safety of treatments available or under investigation for amyloidosis due to mutations in the transthyretin gene (ATTR).
A bibliographic search was carried out in the following electronic databases up to September 2017: PubMed, Cochrane Library and EMBASE. The inclusion criteria were: efficacy and/or safety studies conducted in humans, studies that included treatments, including treatments in the research phase, and studies that included 10 or more patients.
A total of 21 articles were included; 16 were clinical trials, eight of them (50%) phase III trials, and five were observational studies. Of the total number of studies selected, 11 were on tafamidis, four on diflunisal, two on liver transplantation, two on patisiran and two on other therapeutic alternatives. Of the 11 studies related to the drug, the pivotal trial, the results of its two extension studies and an additional post hoc analysis were selected. In addition, two phase III trials were included in specific populations, two phase II studies, one safety study and two observational studies. Regarding the four included studies related to the drug, one was the pivotal trial that gave the indication to diflunisal, another a safety summary of the pivotal trial, and the other two trials were carried out in specific populations, one in a Japanese population and another phase I trial in cardiac amyloidosis in the USA. As far as other alternatives are concerned, of the six studies included in this section, two were related to liver transplantation, two to patisiran and two to different therapeutic alternatives.
Sufficient evidence has not been found that demonstrates superiority among the available oral alternatives, diflunisal or tafamidis, in the treatment of ATTR. Direct comparisons between both drugs and pharmacoeconomic studies would be necessary to select the most efficient treatment.
系统综述文献，分析转甲状腺素蛋白基因（ATTR）突变相关淀粉样变性的现有或正在研究治疗方法的疗效和安全性。
对截至 2017 年 9 月的以下电子数据库进行文献检索：PubMed、Cochrane 图书馆和 EMBASE。纳入标准为：在人体中进行的疗效和/或安全性研究；包括治疗方法的研究，包括研究阶段的治疗方法；以及纳入 10 例或更多患者的研究。
共纳入 21 篇文章；其中 16 项为临床试验，8 项（50%）为 III 期临床试验，5 项为观察性研究。在所选择的研究总数中，有 11 项与 tafamidis 相关，4 项与 diflunisal 相关，2 项与肝移植相关，2 项与 patisiran 相关，2 项与其他治疗方法相关。在与药物相关的 11 项研究中，选择了关键性试验及其两项扩展研究的结果以及另外一项事后分析。此外，还纳入了两项特定人群的 III 期临床试验、两项 II 期研究、一项安全性研究和两项观察性研究。关于与药物相关的四项研究，其中一项为关键性试验，该试验为 diflunisal 提供了适应证，另一项为关键性试验的安全性总结，另外两项试验在特定人群中进行，一项在日本人群中，另一项在美国进行的心脏淀粉样变性 I 期试验。至于其他替代方法，在这部分纳入的 6 项研究中，有两项与肝移植有关，两项与 patisiran 有关，两项与不同的治疗方法有关。
尚未发现有足够证据证明现有口服替代物（diflunisal 或 tafamidis）在治疗 ATTR 方面具有优势。有必要进行这两种药物之间的直接比较以及药物经济学研究，以选择最有效的治疗方法。
