Background
neuropathic, Hereditary transthyretin amyloidosis
DISEASE, HEREDITARY TRANSTHYRETIN AMYLOIDOSIS, ATTRV-PN
Hereditary transthyretin amyloidosis (ATTRv) is a rare, systemic, progressive, and life-threatening disease caused by the misfolding of the transthyretin (TTR) protein and consequent formation of amyloid fibrils, which deposit in organs and tissues throughout the body and disrupt their ability to function [Current gene-silencing treatments for patients with ATTRv-PN aim to slow or halt further damage to organs and tissues, and worsening symptoms, by limiting the production of new TTR amyloid [Further, while the benefit of inotersen on NIS and NIS-LL was shown to be statistically significant at the group level, whether this benefit was clinically meaningful at the level of the individual patient has not yet been investigated. Responder definition (RD) thresholds, also referred to as the minimal clinically important difference (MCID), have been defined as the smallest difference in score that patients would consider a benefit and would warrant a change in their treatment [Based on the evidential gaps described here, this study had three objectives. The first objective was to compare, within patient subgroups defined by key clinical characteristics, mean changes in NIS and NIS-LL total and subscale scores after 65 weeks between patients with ATTRv-PN receiving inotersen or placebo in the NEURO-TTR trial. The second objective was to estimate RD thresholds for NIS and NIS-LL total and subscale scores within this patient sample. The third objective was to examine the efficacy of inotersen for clinically meaningful slowing of neuropathic progression at the level of the individual patient by classifying responders using estimated RD thresholds, and then comparing the proportions of responders at week 65 between patients receiving inotersen and those receiving placebo.