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Peer-reviewedCC BY-NC-NDEuropean Journal of Neurology

Pharmacological Interventions for Hereditary Transthyretin‐Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta‐Analysis

  • Gonçalo Silva Duarte1,2
  • Tiago Luís Gonçalves Neves Machado1
  • Filipe Brogueira Rodrigues1
  • Isabel M. Conceição3,4
  • Davide Pareyson5
  • João Nuno Marques Parracho Guerra da Costa1
  • the Task Force of the EAN/PNS Joint Guideline for the Management of Neurological Manifestations in Hereditary Transthyretin Amyloidosis
5 affiliations
  1. 1Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina Universidade de Lisboa Lisbon Portugal
  2. 2Unidade de Farmacologia Cínica Unidade Local de Saúde de Santa Maria Lisbon Portugal
  3. 3Departamento de Neurociências e Saúde Mental, ULS de Santa Maria CAML Lisbon Portugal
  4. 4Instituto de Fisiologia, Centro de Estudos Egas Moniz, Faculdade de Medicina Universidade de Lisboa Lisbon Portugal
  5. 5Unit of Rare Neurological Diseases, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy
Open at sourceDOICite

Abstract

BACKGROUND: We used network meta-analyses to evaluate the pharmacological interventions for Hereditary Transthyretin-related Amyloidosis with Polyneuropathy (ATTRv-PN). METHODS: We searched Medline, Embase, and Cochrane (June 2025) for randomized trials assessing pharmacological interventions in ATTRv-PN adults. Two reviewers independently screened, extracted data, and assessed risk of bias. Primary efficacy outcomes were mNIS+7 and Norfolk-QoL-DN. Primary safety outcome was serious adverse events (SAE). We used Bayesian hierarchical models. Evidence certainty was assessed using GRADE. RESULTS: Six trials (n = 989) were included (3 at high-risk of bias). Participant ages and disease duration ranged from 52.8 to 62.0 and 1.4 to 3.9 years, respectively. For mNIS+7, data were available for all interventions except tafamidis. All demonstrated statistically significant improvements versus placebo. Vutrisiran (standardized mean difference [SMD] vs. placebo: -1.66; 95% credible interval [CrI]: -2.13 to -1.17) and patisiran (SMD vs. placebo: -1.56; 95% CrI: -1.88 to -1.25) demonstrated improvements compared with diflunisal, eplontersen, and inotersen. For Norfolk-QoL-DN, data were available for all interventions except diflunisal. All except tafamidis demonstrated statistically significant improvements versus placebo. Patisiran (MD vs. placebo: -17.39; 95% CrI: -23.22 to -11.57), vutrisiran (MD vs. placebo: -16.99; 95% CrI: -25.24 to -8.72), and eplontersen (MD vs. placebo: -15.56; 95% CrI: -21.97 to -9.15) demonstrated improvements compared with tafamidis. For SAE, there were no differences between active interventions versus placebo. Confidence in the evidence varied from very low to moderate. CONCLUSION: Gene-silencing therapies were more efficacious, although these findings should be regarded as hypothesis-generating given the scarcity of data, lack of head-to-head trials, and clinical heterogeneity across trials.

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Cite

BibTeXRIS
BibTeX
@article{duarte2026pharmacological,
  title = {{Pharmacological Interventions for Hereditary Transthyretin‐Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta‐Analysis}},
  author = {Gonçalo Silva Duarte and Tiago Luís Gonçalves Neves Machado and Filipe Brogueira Rodrigues and Isabel M. Conceição and Davide Pareyson and João Nuno Marques Parracho Guerra da Costa and the Task Force of the EAN/PNS Joint Guideline for the Management of Neurological Manifestations in Hereditary Transthyretin Amyloidosis},
  journal = {European Journal of Neurology},
  year = {2026},
  month = jun,
  doi = {10.1111/ene.70627},
  url = {https://doi.org/10.1111/ene.70627},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Pharmacological Interventions for Hereditary Transthyretin‐Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta‐Analysis
AU  - Gonçalo Silva Duarte
AU  - Tiago Luís Gonçalves Neves Machado
AU  - Filipe Brogueira Rodrigues
AU  - Isabel M. Conceição
AU  - Davide Pareyson
AU  - João Nuno Marques Parracho Guerra da Costa
AU  - the Task Force of the EAN/PNS Joint Guideline for the Management of Neurological Manifestations in Hereditary Transthyretin Amyloidosis
PY  - 2026
DA  - 2026/06/01
JO  - European Journal of Neurology
DO  - 10.1111/ene.70627
UR  - https://doi.org/10.1111/ene.70627
AB  - BACKGROUND: We used network meta-analyses to evaluate the pharmacological interventions for Hereditary Transthyretin-related Amyloidosis with Polyneuropathy (ATTRv-PN). METHODS: We searched Medline, Embase, and Cochrane (June 2025) for randomized trials assessing pharmacological interventions in ATTRv-PN adults. Two reviewers independently screened, extracted data, and assessed risk of bias. Primary efficacy outcomes were mNIS+7 and Norfolk-QoL-DN. Primary safety outcome was serious adverse events (SAE). We used Bayesian hierarchical models. Evidence certainty was assessed using GRADE. RESULTS: Six trials (n = 989) were included (3 at high-risk of bias). Participant ages and disease duration ranged from 52.8 to 62.0 and 1.4 to 3.9 years, respectively. For mNIS+7, data were available for all interventions except tafamidis. All demonstrated statistically significant improvements versus placebo. Vutrisiran (standardized mean difference [SMD] vs. placebo: -1.66; 95% credible interval [CrI]: -2.13 to -1.17) and patisiran (SMD vs. placebo: -1.56; 95% CrI: -1.88 to -1.25) demonstrated improvements compared with diflunisal, eplontersen, and inotersen. For Norfolk-QoL-DN, data were available for all interventions except diflunisal. All except tafamidis demonstrated statistically significant improvements versus placebo. Patisiran (MD vs. placebo: -17.39; 95% CrI: -23.22 to -11.57), vutrisiran (MD vs. placebo: -16.99; 95% CrI: -25.24 to -8.72), and eplontersen (MD vs. placebo: -15.56; 95% CrI: -21.97 to -9.15) demonstrated improvements compared with tafamidis. For SAE, there were no differences between active interventions versus placebo. Confidence in the evidence varied from very low to moderate. CONCLUSION: Gene-silencing therapies were more efficacious, although these findings should be regarded as hypothesis-generating given the scarcity of data, lack of head-to-head trials, and clinical heterogeneity across trials.
SN  - 1351-5101
SN  - 1468-1331
ER  -