{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina Universidade de Lisboa Lisbon Portugal",
    "Unidade de Farmacologia Cínica Unidade Local de Saúde de Santa Maria Lisbon Portugal",
    "Departamento de Neurociências e Saúde Mental, ULS de Santa Maria CAML Lisbon Portugal",
    "Instituto de Fisiologia, Centro de Estudos Egas Moniz, Faculdade de Medicina Universidade de Lisboa Lisbon Portugal",
    "Unit of Rare Neurological Diseases, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Gonçalo Silva Duarte",
      "orcid": "0000-0001-7802-1897"
    },
    {
      "affs": [
        0
      ],
      "name": "Tiago Luís Gonçalves Neves Machado",
      "orcid": "0000-0001-8930-4382"
    },
    {
      "affs": [
        0
      ],
      "name": "Filipe Brogueira Rodrigues",
      "orcid": "0000-0002-5567-7938"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Isabel M. Conceição",
      "orcid": "0000-0003-0934-9631"
    },
    {
      "affs": [
        4
      ],
      "name": "Davide Pareyson",
      "orcid": "0000-0001-6854-765X"
    },
    {
      "affs": [
        0
      ],
      "name": "João Nuno Marques Parracho Guerra da Costa"
    },
    {
      "name": "the Task Force of the EAN/PNS Joint Guideline for the Management of Neurological Manifestations in Hereditary Transthyretin Amyloidosis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/er5cw1chf8xn2.bib",
  "cited_by": 6,
  "doi": "10.1111/ene.70627",
  "fulltext_url": null,
  "id": "er5cw1chf8xn2",
  "issns": [
    "1351-5101",
    "1468-1331"
  ],
  "landing_url": "https://doi.org/10.1111/ene.70627",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Amyloidosis: Diagnosis, Treatment, Outcomes"
    ]
  ],
  "openalex": "W7164183514",
  "pdf_url": null,
  "pmcid": "PMC13250634",
  "pmid": "42266139",
  "published": "2026-06-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/er5cw1chf8xn2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W7164183514",
      "source": "openalex",
      "url": "https://doi.org/10.1111/ene.70627"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Amyloidosis: Diagnosis, Treatment, Outcomes",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Pharmacological Interventions for Hereditary Transthyretin‐Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta‐Analysis",
  "title_text": "Pharmacological Interventions for Hereditary Transthyretin‐Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta‐Analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T13:20:45Z",
  "url": "https://research.draconitic.com/paper/er5cw1chf8xn2",
  "venue": "European Journal of Neurology",
  "versions": []
}