Evidence map›Paper›PMID 32654212›Full record

Trial reportMuscle & nerve2020

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 and 2 more

Registry-linked trialOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Muscle & nerve, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01737398 (A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01737398 phase2 / phase3completednot on this map

A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (NEURO-TTR Study)

TypeinterventionalSponsorIonis Pharmaceuticals, Inc.Ran2013 to 2017Enrolled173ConditionsFAP, Familial Amyloid Polyneuropathy, TTR, TransthyretinArmsInotersen, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Review
  6. Review
  7. Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis.Journal of neurology, neurosurgery, and psychiatry · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

P James B DyckDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0003-0212-8254
John C KincaidDepartment of Neurology, Indiana University, Indianapolis, Indiana, USA.
Janice F WiesmanDepartment of Neurology, New York University, New York, New York, USA.
Michael PolydefkisDepartment of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
William J LitchyDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Michelle L MauermannDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Elizabeth J AckermannOtonomy, Inc., San Diego, California, USA.
Spencer GuthrieAurora Bio, San Francisco, California, USA.
Michael PollockAkcea Therapeutics, Inc., Cambridge, Massachusetts, USA.
Shiangtung W JungIonis Pharmaceuticals, Inc., Carlsbad, California, USA.
Brenda F BakerIonis Pharmaceuticals, Inc., Carlsbad, California, USA.
Peter J DyckDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Mayo Clinic · USAkebia Therapeutics (United States) · USIonis Pharmaceuticals (United States) · USIndiana University Health · USJohns Hopkins University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionInotersen, 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.

methodsAdults 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.

resultsAll 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.

Indexed as

Amyloid Neuropathies, FamilialDouble-Blind MethodFemaleHeart RateHumansLower ExtremityMaleMiddle AgedMuscle WeaknessOligonucleotidesOligonucleotides, AntisenseReflexTreatment OutcomeInotersenOligonucleotidesOligonucleotides, AntisenseamyloidosishATTRinotersenlower limb functionmNIS+7

Identifiers

PMID32654212
PMCPMC7540053
OpenAlexW3041960505

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.