Citations

AbstractIntroductionAmyloid 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.MethodsA PubMed search from 2008 to September 2018 was conducted to review the literature on ATTR.ResultsUntil 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.ConclusionsImportant 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.

ABSTRACTIntroductionPolyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial.MethodsWe assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis) and its subscores and correlation with disability and health scores.ResultsThe mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests.ConclusionsSpecially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901–911, 2017