Evidence map›Paper›PMID 38512694›Full record

ArticleNeurology and therapy2024

Impact of Baseline Neuropathy Severity on Vutrisiran Treatment Response in the Phase 3 HELIOS-A Study.

Marco Luigetti, Dianna Quan, John L Berk, Isabel Conceição, Yohei Misumi, Chi-Chao Chao, Shaun Bender, Emre Aldinc, John Vest, David Adams

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03759379 (HELIOS-A), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 38% 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.

NCT03759379 phase3completednot on this map

HELIOS-A: A Phase 3 Global, Randomized, Open-label Study to Evaluate the Efficacy and Safety of ALN-TTRSC02 in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)

TypeinterventionalSponsorAlnylam PharmaceuticalsRan2019 to 2025Enrolled164ConditionsAmyloidosis, Hereditary, Transthyretin AmyloidosisArmsPatisiran, Vutrisiran
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Trial
  2. Review
  3. 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

10 authors at 8 institutions in 6 countries.

Marco LuigettiDipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy. mluigetti@gmail.com.ORCID http://orcid.org/0000-0001-7539-505X
Dianna QuanDepartment of Neurology, University of Colorado Anschutz, Aurora, CO, USA.
John L BerkBoston Medical Center, Boston, MA, USA.
Isabel ConceiçãoDepartment of Neurology, CHULN, Hospital Santa Maria and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Yohei MisumiDepartment of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Chi-Chao ChaoDepartment of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Shaun BenderAlnylam Pharmaceuticals, Cambridge, MA, USA.
Emre AldincAlnylam Pharmaceuticals, Cambridge, MA, USA.
John VestAlnylam Pharmaceuticals, Cambridge, MA, USA.
David AdamsNeurology Department, Université Paris-Saclay, U1195, INSERM, AP-HP, CHU Bicêtre, Le Kremlin Bicêtre, France.
Alnylam Pharmaceuticals (United States) · USBoston Medical Center · USInserm · FRKumamoto University · JPNational Taiwan University Hospital · TWUniversità Cattolica del Sacro Cuore · ITUniversity of Colorado Anschutz Medical Campus · USUniversity of Lisbon · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionHereditary transthyretin (ATTRv, v for variant) amyloidosis is a rare, progressive, fatal disease with multisystem manifestations, caused by pathogenic variants in the transthyretin (TTR) gene. Vutrisiran, an RNA interference therapeutic that results in rapid TTR knockdown, improved neuropathy and quality of life (QOL) versus external placebo in patients with ATTRv amyloidosis with polyneuropathy in the phase 3 HELIOS-A study (NCT03759379). This post hoc analysis evaluates the impact of baseline neuropathy severity on response to vutrisiran treatment.

methodsPatients were randomized (3:1) to vutrisiran (n = 122; 25 mg subcutaneous injection once every 3 months) or patisiran (n = 42; 0.3 mg/kg intravenous infusion once every 3 weeks), which served as a reference group. In this post hoc analysis, patients were grouped into quartiles of increasing baseline Neuropathy Impairment Score (NIS): Quartile (Q)1 ≥ 5.0 to ≤ 20.5; Q2 > 20.5 to ≤ 44.1; Q3 > 44.1 to ≤ 73.1; Q4 > 73.1 to ≤ 127.0. Mean change from baseline to Month 18 was summarized by quartile for a range of efficacy endpoints.

resultsAcross all baseline NIS quartiles, vutrisiran demonstrated benefit versus external placebo in measures of neuropathy severity (modified NIS + 7), QOL (Norfolk Quality of Life-Diabetic Neuropathy), disability (Rasch-built Overall Disability Scale), gait speed (10-m walk test), and nutritional status (modified body mass index). Overall, patients in lower versus higher NIS quartiles (less severe neuropathy) at baseline maintained better scores at Month 18. The external placebo group progressively worsened in all measures at Month 18.

conclusionsVutrisiran demonstrated benefit in neurologic function and other key efficacy measures versus external placebo across all four baseline neuropathy severity quartiles. Patients initiating vutrisiran earlier in their disease course retained the highest neurologic function level after 18 months, highlighting the importance of early diagnosis and treatment. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03759379.

Indexed as

ATTRv amyloidosisBaseline NIS quartilesDisabilityNeuropathy severityNutritional statusPolyneuropathyQuality of lifeRNA interferenceVutrisiran

Identifiers

PMID38512694
PMCPMC11136903
OpenAlexW4393037980

What Socratic 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 Socratic graph.