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

P James B Dyck, John C Kincaid, Janice F Wiesman, Michael Polydefkis, William J Litchy, Michelle L Mauermann, Elizabeth J Ackermann, Spencer Guthrie, Michael Pollock, Shiangtung W Jung, Brenda F Baker, Peter J Dyck, P James B Dyck, John C Kincaid, Janice F Wiesman, Michael Polydefkis, William J Litchy, Michelle L Mauermann, Elizabeth J Ackermann, Spencer Guthrie, Michael Pollock, Shiangtung W Jung, Brenda F Baker, Peter J Dyck

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.

© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.

Figures

FIGURE 1
FIGURE 1
Select mNIS+7 components analyzed as upper limb and lower limb LSM, least‐squares mean; mNIS+7, modified neuropathy impairment scale +7 neurophysiologic tests. Note: Increase in score denotes worse neuropathic deficit [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Change in normal deviates of the five attributes of nerve conduction. CMAP, compound muscle action potential; LSM, least‐squares mean; ND, normal deviate; SNAP, sensory nerve action potential. Note: Increase in score denotes worse neuropathic deficit [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Change in lower limb function score over time. LSM, least‐squares mean [Color figure can be viewed at wileyonlinelibrary.com]

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Source: PubMed

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