Mayo Clinic, Rochester, Minnesota.
Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
Brain Behav. 2019 Sep;9(9):e01371. doi: 10.1002/brb3.1371. Epub 2019 Aug 1.
Amyloid transthyretin amyloidosis (ATTR) is a progressive and often fatal disease caused by the buildup of mutated (hereditary ATTR [hATTR]; also known as ATTR variant [ATTRv]) or normal transthyretin (wild-type ATTR) throughout the body. Two new therapies-inotersen, an antisense oligonucleotide therapy, and patisiran, an RNA interference therapy-received marketing authorization and represent a significant advance in the treatment of amyloidosis. Herein, we describe the clinical presentation of ATTR, commonly used procedures in its diagnosis, and current treatment landscape for ATTR, with a focus on hATTR.
A PubMed search from 2008 to September 2018 was conducted to review the literature on ATTR.
Until recently, there have been few treatment options for polyneuropathy of hATTR. Inotersen and patisiran substantially reduce the amyloidogenic precursor protein transthyretin and have demonstrated efficacy in patients with early- and late-stage disease and in slowing or improving neuropathy progression. In contrast, established therapies, such as liver transplantation, typically reserved for patients with early-stage disease, and tafamidis, indicated for the treatment of early-stage disease in Europe, or diflunisal, a nonsteroidal anti-inflammatory drug that is used off-label, are associated with side effects and/or unclear efficacy in certain patient populations. Thus, inotersen and patisiran are positioned to be the preferred therapeutic modalities.
Important differences between inotersen and patisiran, including formulation, dosing, requirements for premedications, and safety monitoring, require an understanding and knowledge of each treatment for informed decision making.
淀粉样变性转甲状腺素蛋白（ATTR）是一种进行性且通常致命的疾病，由突变（遗传性 ATTR [hATTR]；也称为 ATTR 变体 [ATTRv]）或正常转甲状腺素蛋白在全身蓄积引起。两种新的疗法——反义寡核苷酸疗法 inotersen 和 RNA 干扰疗法 patisiran——获得了市场批准，代表着在淀粉样变性治疗方面的重大进展。本文描述了 ATTR 的临床表现、常用的诊断方法以及当前针对 ATTR 的治疗方法，重点是 hATTR。
对 2008 年至 2018 年 9 月的 PubMed 文献进行了检索，以综述 ATTR 的文献。
直到最近，hATTR 的多发性神经病治疗选择有限。Inotersen 和 patisiran 可显著减少淀粉样前体蛋白转甲状腺素蛋白，并已在早期和晚期疾病患者以及减缓或改善神经病变进展方面显示出疗效。相比之下，肝移植等既定疗法通常保留给早期疾病患者，tafamidis 则在欧洲被批准用于早期疾病的治疗，而非甾体抗炎药 diflunisal 则在标签外用于治疗，这些疗法与某些患者群体的副作用和/或疗效不明确有关。因此，inotersen 和 patisiran 有望成为首选的治疗方法。
inotersen 和 patisiran 之间存在重要差异，包括制剂、剂量、用药前准备要求和安全性监测，因此需要了解和掌握每种治疗方法，以便做出明智的决策。
