{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:51:54Z","timestamp":1775713914539,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"Abstract<\/jats:title>Background and purpose<\/jats:title>Hereditary transthyretin (TTR) amyloidosis (ATTRv) is a dominantly inherited, adult\u2010onset, progressive, and fatal disease caused by mutations in the transthyretin<\/jats:italic> gene. Therapeutic agents approved for this disease include the TTR stabilizer tafamidis and the gene\u2010silencing drugs patisiran and inotersen. Inotersen is an antisense oligonucleotide that suppresses the hepatic production of transthyretin. After European Medical Agency approval in 2018, an early\u2010access program was opened in Italy, and in this article, we present the long\u2010term outcome of a cohort of Italian ATTRv patients who received inotersen within this program.<\/jats:p><\/jats:sec>Methods<\/jats:title>This is a multicenter, observational, retrospective study of patients affected by ATTRv that started inotersen during the early\u2010access program. The primary end point was safety. Secondary end points included change from baseline in familial amyloid polyneuropathy (FAP) stage, Polyneuropathy Disability, Neuropathy Impairment Scale, Compound Autonomic Dysfunction Test, Norfolk Quality of Life\u2013Diabetic Neuropathy, troponin, N\u2010terminal pro\u2013brain natriuretic peptide, interventricular septum thickness, and body mass index.<\/jats:p><\/jats:sec>Results<\/jats:title>In total, 23 patients were enrolled. No patient permanently discontinued the treatment because of thrombocytopenia, and no cases of severe thrombocytopenia were observed. Five patients discontinued the treatment permanently because of voluntary withdrawal (two patients), renal failure after infective pyelonephritis, not related to inotersen, drug\u2010related hypotension, and amyloid\u2010negative crescentic glomerulonephritis. In seven patients, dosing frequency was reduced to every 2\u00a0weeks due to recurrent thrombocytopenia. Considering the FAP stage, only two patients worsened, whereas the other 21 patients remained stable until the last follow\u2010up available.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The long\u2010term safety profile of inotersen is favorable. Neurologic disease severity at baseline is the main factor associated with progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15325","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T08:05:39Z","timestamp":1647331539000},"page":"2148-2155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Real\u2010life experience with inotersen in hereditary transthyretin amyloidosis with late\u2010onset phenotype: Data from an early\u2010access program in Italy"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-505X","authenticated-orcid":false,"given":"Marco","family":"Luigetti","sequence":"first","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS UOC Neurologia Rome Italy"},{"name":"Department of Neuroscience Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Antonini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mental Health and Sensory Organs Faculty of Medicine and Psychology Sant\u2019Andrea Hospital Sapienza University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Di Paolantonio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Gentile","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases Department of Clinical and Experimental Medicine University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Grandis","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal Infantile Sciences University of Genova Genoa Italy"},{"name":"San Martino Polyclinic Hospital, Scientific Institute for Research and Health Care Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mental Health and Sensory Organs Faculty of Medicine and Psychology Sant\u2019Andrea Hospital Sapienza University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Lozza","sequence":"additional","affiliation":[{"name":"Amyloidosis Research and Treatment Center San Matteo Polyclinic Foundation, Scientific Institute for Research and Health Care Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-3744","authenticated-orcid":false,"given":"Fiore","family":"Manganelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive and Odontostomatological Science University of Naples \"Federico II\" Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Mazzeo","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases Department of Clinical and Experimental Medicine University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Mussinelli","sequence":"additional","affiliation":[{"name":"Amyloidosis Research and Treatment Center San Matteo Polyclinic Foundation, Scientific Institute for Research and Health Care Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filomena","family":"My","sequence":"additional","affiliation":[{"name":"UOC Neurologia Vito Fazzi Hospital Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Obici","sequence":"additional","affiliation":[{"name":"Amyloidosis Research and Treatment Center San Matteo Polyclinic Foundation, Scientific Institute for Research and Health Care Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Maria\u00a0Pennisi","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Neurological Diseases\u2013Neurology Unit San Filippo Neri Hospital Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-3141","authenticated-orcid":false,"given":"Marina","family":"Romozzi","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS UOC Neurologia Rome Italy"},{"name":"Department of Neuroscience Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Russo","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases Department of Clinical and Experimental Medicine University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6635-4985","authenticated-orcid":false,"given":"Mario","family":"Sabatelli","sequence":"additional","affiliation":[{"name":"Centro Clinico NEMO Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-7566","authenticated-orcid":false,"given":"Alessandro","family":"Salvalaggio","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of Padova Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3048-1453","authenticated-orcid":false,"given":"Matteo","family":"Tagliapietra","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine, and Movement Sciences University of Verona Verona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-4577","authenticated-orcid":false,"given":"Stefano","family":"Tozza","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive and Odontostomatological Science University of Naples \"Federico II\" Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(11)70246\u20100"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2020.1794807"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010020\u201004889\u20102"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12451"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/tcrm.S219979"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11050545"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716793"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716153"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182661eb1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14285"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883\u2010021\u201002094\u2010y"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11040515"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001870"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.283815"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26515"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15325","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.15325","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T20:49:57Z","timestamp":1692737397000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.15325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,28]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/ene.15325"],"URL":"https:\/\/doi.org\/10.1111\/ene.15325","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,28]]},"assertion":[{"value":"2022-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}