mNIS+7 and lower limb function in inotersen treatment of hereditary transthyretin-mediated amyloidosis

Muscle Nerve. 2020 Oct;62(4):502-508. doi: 10.1002/mus.27022. Epub 2020 Aug 13.

Abstract

Introduction: Inotersen, an antisense oligonucleotide inhibitor of transthyretin (TTR) protein production, demonstrated significant benefit versus placebo in the modified Neuropathy Impairment Score (NIS) +7 neurophysiologic tests (mNIS+7) in patients with hereditary TTR-mediated amyloidosis (hATTR) with polyneuropathy. This analysis assessed the mNIS+7 components by anatomic location and the lower limb function (LLF) test.

Methods: Adults with hATTR in the NEURO-TTR trial (NCT01737398) were randomly assigned to receive weekly doses of subcutaneous inotersen 300 mg or placebo for 65 weeks. The mNIS+7 and LLF were assessed at 35 and 66 weeks.

Results: All major mNIS+7 components (muscle weakness, muscle stretch reflexes, sensation) and the LLF showed significant efficacy in patients receiving inotersen versus placebo; however, NIS-reflexes (upper limb), touch pressure (upper and lower limbs), and heart rate during deep breathing did not show significant effects.

Discussion: The results of this analysis reinforce the beneficial effect of inotersen on slowing neuropathy progression in patients with hATTR polyneuropathy.

Keywords: amyloidosis; hATTR; inotersen; lower limb function; mNIS+7.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / physiopathology
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Humans
  • Lower Extremity / physiopathology*
  • Male
  • Middle Aged
  • Muscle Weakness / drug therapy*
  • Muscle Weakness / physiopathology
  • Oligonucleotides / pharmacology
  • Oligonucleotides / therapeutic use*
  • Oligonucleotides, Antisense / pharmacology
  • Oligonucleotides, Antisense / therapeutic use*
  • Reflex / drug effects
  • Treatment Outcome

Substances

  • Oligonucleotides
  • Oligonucleotides, Antisense
  • Inotersen

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT01737398