{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:19:20Z","timestamp":1789057160710,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We used network meta\u2010analyses to evaluate the pharmacological interventions for Hereditary Transthyretin\u2010related Amyloidosis with Polyneuropathy (ATTRv\u2010PN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched Medline, Embase, and Cochrane (June 2025) for randomized trials assessing pharmacological interventions in ATTRv\u2010PN adults. Two reviewers independently screened, extracted data, and assessed risk of bias. Primary efficacy outcomes were mNIS+7 and Norfolk\u2010QoL\u2010DN. Primary safety outcome was serious adverse events (SAE). We used Bayesian hierarchical models. Evidence certainty was assessed using GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six trials (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009989) were included (3 at high\u2010risk of bias). Participant ages and disease duration ranged from 52.8 to 62.0 and 1.4 to 3.9\u2009years, 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: \u22121.66; 95% credible interval [CrI]: \u22122.13 to \u22121.17) and patisiran (SMD vs. placebo: \u22121.56; 95% CrI: \u22121.88 to \u22121.25) demonstrated improvements compared with diflunisal, eplontersen, and inotersen. For Norfolk\u2010QoL\u2010DN, data were available for all interventions except diflunisal. All except tafamidis demonstrated statistically significant improvements versus placebo. Patisiran (MD vs. placebo: \u221217.39; 95% CrI: \u221223.22 to \u221211.57), vutrisiran (MD vs. placebo: \u221216.99; 95% CrI: \u221225.24 to \u22128.72), and eplontersen (MD vs. placebo: \u221215.56; 95% CrI: \u221221.97 to \u22129.15) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gene\u2010silencing therapies were more efficacious, although these findings should be regarded as hypothesis\u2010generating given the scarcity of data, lack of head\u2010to\u2010head trials, and clinical heterogeneity across trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70627","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:54:50Z","timestamp":1781078090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological Interventions for Hereditary Transthyretin\u2010Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta\u2010Analysis"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7802-1897","authenticated-orcid":false,"given":"Gon\u00e7alo S","family":"Duarte","sequence":"first","affiliation":[{"name":"Unidade de Farmacologia C\u00ednica Unidade Local de Sa\u00fade de Santa Maria  Lisbon Portugal"},{"name":"Laborat\u00f3rio de Farmacologia Cl\u00ednica e Terap\u00eautica, Faculdade de Medicina Universidade de Lisboa  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8930-4382","authenticated-orcid":false,"given":"Tiago Lu\u00eds Gon\u00e7alves Neves","family":"Machado","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Cl\u00ednica e Terap\u00eautica, Faculdade de Medicina Universidade de Lisboa  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5567-7938","authenticated-orcid":false,"given":"Filipe B","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Cl\u00ednica e Terap\u00eautica, Faculdade de Medicina Universidade de Lisboa  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-9631","authenticated-orcid":false,"given":"Isabel","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Neuroci\u00eancias e Sa\u00fade Mental, ULS de Santa Maria CAML  Lisbon Portugal"},{"name":"Instituto de Fisiologia, Centro de Estudos Egas Moniz, Faculdade de Medicina Universidade de Lisboa  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-765X","authenticated-orcid":false,"given":"Davide","family":"Pareyson","sequence":"additional","affiliation":[{"name":"Unit of Rare Neurological Diseases, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Nuno Marques Parracho Guerra","family":"da Costa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Cl\u00ednica e Terap\u00eautica, Faculdade de Medicina Universidade de Lisboa  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Task Force of the EAN\/PNS Joint Guideline for the Management of Neurological Manifestations in Hereditary Transthyretin Amyloidosis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0210-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222313158"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.596"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12153"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/msj.21352"},{"key":"e_1_2_10_7_1","first-page":"S107","article-title":"Hereditary ATTR Amyloidosis: Burden of Illness and Diagnostic Challenges","volume":"23","author":"Gertz M. 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