Evidence map›Paper›PMID 32343462›Full record

Trial reportEuropean journal of neurology2020

Early data on long-term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis: a 2-year update from the open-label extension of the NEURO-TTR trial.

T H Brannagan, A K Wang, T Coelho, M Waddington Cruz, M J Polydefkis, P J Dyck, V Plante-Bordeneuve, J L Berk, F Barroso, G Merlini and 9 more

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

Trial report in European journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02175004 (An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy), which is not on this map. Cited by 44 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 2 pooled it
4.3field-weighted citation impact, top 5% 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.

NCT02175004 phase3completednot on this map

An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (FAP)

TypeinterventionalSponsorIonis Pharmaceuticals, Inc.Ran2014 to 2021Enrolled135ConditionsFAP, Familial Amyloid Polyneuropathy, TTR, TransthyretinArmsInotersen
3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Review
  6. Review
  7. Inotersen for the Treatment of Hereditary Transthyretin Amyloidosis.Methods in molecular biology (Clifton, N.J.) · 2026
    Review
  8. Article
  9. Review
  10. RNA therapeutics in cardiovascular medicine.Current opinion in cardiology · 2025
    Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Serum neurofilament light chain levels correlate with small fiber related parameters in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Article
  16. Gene-based therapies for neuromuscular disorders.Arquivos de neuro-psiquiatria · 2024
    Article
  17. Review
  18. Article
  19. Article
  20. Article
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

19 authors at 15 institutions in 6 countries.

T H BrannaganColumbia University Medical Center, New York, NY, USA.ORCID 0000-0002-1812-8331
A K WangUniversity of California, Irvine, Orange, CA, USA.
T CoelhoCentro Hospitalar do Porto, Porto, Portugal.
M Waddington CruzCEPARM, Amyloidosis Referral Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
M J PolydefkisJohns Hopkins University, Baltimore, MD, USA.
P J DyckMayo Clinic, Rochester, MN, USA.
V Plante-BordeneuveCHU Henri Mondor, Creteil, France.
J L BerkBoston University, Boston, MA, USA.
F BarrosoFLENI, Buenos Aires, Argentina.
G MerliniAmyloidosis Center, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
I ConceiçãoCHULN, Hospital Santa Maria and Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
S G HughesIonis Pharmaceuticals, Inc., Carlsbad, CA, USA.
J KwohIonis Pharmaceuticals, Inc., Carlsbad, CA, USA.
S W JungIonis Pharmaceuticals, Inc., Carlsbad, CA, USA.
S GuthrieAurora Bio, San Francisco, CA, USA.
M PollockAkcea Therapeutics, Inc., Boston, MA, USA.
M D BensonIndiana University School of Medicine, Indianapolis, IN, USA.
M GertzMayo Clinic, Rochester, MN, USA.
NEURO-TTR open-label extension investigators
Ionis Pharmaceuticals (United States) · USMayo Clinic in Arizona · USAkebia Therapeutics (United States) · USAurora University · USBoston University · USCentre Hospitalier Universitaire Henri-Mondor · FRCentro Hospitalar do Porto · PTColumbia University Irving Medical Center · USFundación para la Lucha contra las Enfermedades Neurológicas de la Infancia · ARIndiana University School of MedicineJohns Hopkins University · USUniversidade Federal do Rio de Janeiro · BRUniversity of California, Irvine · USUniversity of Lisbon · PTUniversity of Pavia · IT

Funding

Pathogenesis and Treatment of AA AmyloidosisI01CX001631 · VA · RLR VA MEDICAL CENTER · PI BENSON, MERRILL D · 2018 to 2021
–
CSRD VA I01 CX001631Ionis Pharmaceuticals, Inc.
6 · The paper itself

Abstract

background and purposeHereditary transthyretin (hATTR) amyloidosis causes progressive polyneuropathy resulting from transthyretin (TTR) amyloid deposition throughout the body, including the peripheral nerves. The efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, were demonstrated in the pivotal NEURO-TTR study in patients with hATTR polyneuropathy. Here, the long-term efficacy and safety of inotersen are assessed in an ongoing open-label extension (OLE) study.

methodsPatients who completed NEURO-TTR were eligible to enroll in the OLE (NCT02175004). Efficacy assessments included the modified Neuropathy Impairment Score plus seven neurophysiological tests composite score (mNIS + 7), the Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) questionnaire total score and the Short-Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score. Safety and tolerability were also assessed.

resultsOverall, 97% (135/139) of patients who completed NEURO-TTR enrolled in the OLE. Patients who received inotersen for 39 cumulative months in NEURO-TTR and the OLE continued to show benefit; patients who switched from placebo to inotersen in the OLE demonstrated improvement or stabilization of neurological disease progression by mNIS + 7, Norfolk QOL-DN and SF-36 PCS. No new safety concerns were identified. There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of inotersen exposure.

conclusionInotersen slowed disease progression and reduced deterioration of quality of life in patients with hATTR polyneuropathy. Early treatment with inotersen resulted in greater long-term disease stabilization than delayed initiation. Routine platelet and renal safety monitoring were effective; no new safety signals were observed.

Indexed as

Amyloid Neuropathies, FamilialQuality of LifeFemaleHumansMaleMiddle AgedOligonucleotidesPrealbuminInotersenOligonucleotidesPrealbumingenetic and inherited disordersperipheral neuropathiespolyneuropathy

Identifiers

PMID32343462
PMCPMC7496583
OpenAlexW3018892538

What OpenQuestion holds

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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.