{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:13:01Z","timestamp":1776276781650,"version":"3.50.1"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Nos. 81774085, 82100439"],"award-info":[{"award-number":["Nos. 81774085, 82100439"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shandong Provincial Science and Technology Department Youth Science Fund Project","award":["ZR2022QH154, ZR2024QH242"],"award-info":[{"award-number":["ZR2022QH154, ZR2024QH242"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M751844"],"award-info":[{"award-number":["2024M751844"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vutrisiran is a double-stranded siRNA targeting transthyretin mRNA, primarily for the treatment of transthyretin-mediated amyloidosis (ATTR) with polyneuropathy. Understanding its safety in real-world settings is crucial for achieving optimal treatment outcomes for patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study assessed the safety of vutrisiran for clinical use by analyzing all adverse drug reaction (ADR) reports in WHO-VigiAccess and U.S. Food and Drug Administration\u2019s Adverse Event Reporting System (FAERS) databases with vutrisiran as the primary suspected drug and by using four disproportionality analysis and Bayesian information component. Weibull distribution was also utilized to predict the time of occurrence of ADR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During the research process, WHO-VigiAccess reported 721 adverse reaction reports related to vutrisiran, while FAERS documented 732 ADR reports. The analysis revealed that: this study not only demonstrated known adverse reactions such as injection site reactions, such as redness, pain, or swelling at the injection site; systemic reactions like fatigue and myalgia; pain in extremity; and potential risks associated with reduced vitamin A levels, but also detected potential safety signals related to drug such as night blindness and cardiac pacemaker insertion. Furthermore, it was observed that in both the WHO-VigiAccess and FAERS databases, the highest reporting rates of ADR were found in the category of general disorders and administration site conditions. It also confirms the importance of monitoring the occurrence of adverse reactions within one year after drug treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study identified several known ADRs and detected potential positive signals that may be associated with the drug. These research results provide clinicians with more information to consider and monitor adverse reactions in patients with ATTR-related polyneuropathy after treatment with vutrisiran, offering more evidence for its safety in real-world settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347417","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:32:52Z","timestamp":1776274372000},"page":"e0347417","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the real-world safety of vutrisiran for transthyretin-mediated amyloidosis with polyneuropathy: Based on WHO-VigiAccess and FAERS databases"],"prefix":"10.1371","volume":"21","author":[{"given":"Weiwei","family":"Tong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0705-5668","authenticated-orcid":true,"given":"Yaxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingli","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruonan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanliang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jidang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chigang","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"pone.0347417.ref001","author":"FDA"},{"issue":"7","key":"pone.0347417.ref002","doi-asserted-by":"crossref","first-page":"370","DOI":"10.4330\/wjc.v16.i7.370","article-title":"Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis","volume":"16","author":"C Kourek","year":"2024","journal-title":"World J Cardiol"},{"issue":"1","key":"pone.0347417.ref003","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jns.12153","article-title":"\u201cRed-flag\u201d symptom clusters in transthyretin familial amyloid polyneuropathy","volume":"21","author":"I Concei\u00e7\u00e3o","year":"2016","journal-title":"J Peripher Nerv Syst"},{"issue":"8","key":"pone.0347417.ref004","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3109\/07853890.2015.1068949","article-title":"Evolving landscape in the management of transthyretin amyloidosis","volume":"47","author":"PN Hawkins","year":"2015","journal-title":"Ann Med"},{"issue":"9","key":"pone.0347417.ref005","doi-asserted-by":"crossref","first-page":"102066","DOI":"10.1016\/j.jacadv.2025.102066","article-title":"Vutrisiran in transthyretin amyloidosis: A pooled safety analysis of HELIOS-A and HELIOS-B","volume":"4","author":"RM Witteles","year":"2025","journal-title":"JACC Adv"},{"issue":"2","key":"pone.0347417.ref006","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/cpt.1974","article-title":"Single-dose pharmacokinetics and pharmacodynamics of transthyretin targeting n-acetylgalactosamine-small interfering ribonucleic acid conjugate, vutrisiran, in healthy subjects","volume":"109","author":"BA Habtemariam","year":"2021","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"pone.0347417.ref007","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13023-017-0726-x","article-title":"Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: Red-flag symptom clusters and treatment algorithm","volume":"13","author":"Y Sekijima","year":"2018","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"pone.0347417.ref008","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/nat.2018.0736","article-title":"GalNAc-siRNA Conjugates: Leading the way for delivery of RNAi Therapeutics","volume":"28","author":"AD Springer","year":"2018","journal-title":"Nucleic Acid Ther"},{"issue":"18","key":"pone.0347417.ref009","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1056\/NEJMc2501792","article-title":"Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. 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Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: A randomized clinical trial. 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