Evidence mapPaperPMID 31728713Full record

Trial reportJournal of neurology2020

Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.

Alejandra González-Duarte, John L Berk, Dianna Quan, Michelle L Mauermann, Hartmut H Schmidt, Michael Polydefkis, Márcia Waddington-Cruz, Mitsuharu Ueda, Isabel M Conceição, Arnt V Kristen and 9 more

Erratum issuedOpen access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.1field-weighted citation impact, top 12% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 59 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Cost analysis of transthyretin amyloid cardiomyopathy in heart failure patients with preserved ejection fraction in Spain.The European journal of health economics : HEPAC : health economics in prevention and care · 2026
    Article
  6. Article
  7. Impact of autonomic dysfunction on cardiovascular outcomes among patients with ATTR cardiomyopathy: insights from the COMPASS-31.Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · 2025
    Article
  8. Review
  9. Article
  10. Long-term treatment of hereditary transthyretin amyloidosis with patisiran: multicentre, real-world experience in Italy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Observational
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. RNA Targeting and Gene Editing Strategies for Transthyretin Amyloidosis.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 15 institutions in 7 countries.

Alejandra González-DuarteInstituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Sección XVI, Tlalpan, CdMx, CP 01400, México City, Mexico. gonzalezduarte@aol.com.
John L BerkBoston Medical Center, Boston, MA, USA.
Dianna QuanUniversity of Colorado, Denver, CO, USA.
Michelle L MauermannMayo Clinic, Rochester, MN, USA.
Hartmut H SchmidtUniversity of Münster, Münster, Germany.
Michael PolydefkisJohns Hopkins University School of Medicine, Baltimore, MD, USA.
Márcia Waddington-CruzHospital Universitário Clementino Fraga Filho-UFRJ, Rio de Janeiro, Brazil.
Mitsuharu UedaKumamoto University Hospital, Kumamoto, Japan.
Isabel M ConceiçãoCHULN, Hospital de Santa Maria and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Arnt V KristenUniversity of Heidelberg, Heidelberg, Germany.
Teresa CoelhoHospital de Santo António, Centro Hospitalar Universitário Do Porto, Porto, Portugal.
Cécile A CauquilAP-HP Université Paris Saclay, CHU Bicêtre, Le Kremlin Bicêtre, France.
Céline TardUniversité de Lille, Lille, France.
Madeline MerkelAlnylam Pharmaceuticals, Cambridge, MA, USA.
Emre AldincAlnylam Pharmaceuticals, Cambridge, MA, USA.
Jihong ChenAlnylam Pharmaceuticals, Cambridge, MA, USA.
Marianne T SweetserAlnylam Pharmaceuticals, Cambridge, MA, USA.
Jing Jing WangAlnylam Pharmaceuticals, Cambridge, MA, USA.
David AdamsAP-HP, Université Paris Saclay, CHU Bicêtre, Université Paris-Sud, INSERM 1195, Paris, France.
Alnylam Pharmaceuticals (United States) · USBicêtre Hospital · FRBoston Medical Center · USHeidelberg University · DEHospital de Santo António · PTHospital Universitário Clementino Fraga Filho · BRInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXJohns Hopkins Medicine · USKumamoto University Hospital · JPMayo Clinic in Arizona · USUniversité de Lille · FRUniversité Paris-Sud · FRUniversity of Colorado Denver · USUniversity of Lisbon · PTUniversity of Münster · DE

Funding

Alnylam Pharmaceuticals N/A
6 · The paper itself

Abstract

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

Indexed as

AdultAmyloid Neuropathies, FamilialAutonomic Nervous System DiseasesDouble-Blind MethodFemaleHumansMaleMiddle AgedPolyneuropathiesQuality of LifeRNAi TherapeuticsRNA, Small InterferingpatisiranRNA, Small InterferingAutonomic nervous system diseasesHereditary transthyretin-mediated amyloidosisPatisiranPolyneuropathySmall interfering ribonucleic acid (siRNA)Transthyretin

Identifiers

PMID31728713
PMCPMC7035216
OpenAlexW2986750111

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.