{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:06:04Z","timestamp":1790805964641,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013669","name":"Ionis Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013669","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Hereditary transthyretin\u2010mediated amyloidosis with polyneuropathy (hATTR\u2010PN) progressively affects patients' functionality and compromises health\u2010related quality of life (HRQL). The aim of this study was to quantify the projected long\u2010term treatment effects of inotersen vs placebo on HRQL measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The inotersen phase 2\/3 randomized, double\u2010blind, placebo\u2010controlled trial NEURO\u2010TTR (NCT01737398, 65\u2009weeks) and its subsequent open\u2010label extension (OLE; NCT02175004, 104\u2009weeks) included 172 (112 inotersen and 60 placebo) patients. Placebo double\u2010blind period and overall inotersen\u2010inotersen (double\u2010blind\/OLE) treatment period (170\u2009weeks) data were used to extrapolate the long\u2010term placebo\u2010placebo effect using mixed\u2010effects models with repeated measures. Changes from baseline in the Norfolk Quality of Life\u2010Diabetic Neuropathy (QoL\u2010DN) and 36\u2010Item Short Form Health Survey version 2 (SF\u201036v2) in hATTR\u2010PN were estimated. Differences in changes were compared between the inotersen\u2010inotersen and extrapolated placebo\u2010placebo arms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inotersen\u2010inotersen patients maintained their HRQL with an observed change ranging from 10.3% improvement (Norfolk QoL\u2010DN item \u201cPain kept you awake at night\u201d) to 11.6% deterioration (SF\u201036v2 Activities of Daily Living subdomain). The extrapolated placebo\u2010placebo results suggest greater deterioration over time compared with inotersen\u2010inotersen treatment on Norfolk QoL\u2010DN total score (23.6; 95% confidence interval [CI], 8.9\u201038.3; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01), Activities of Daily Living (4.6; 95% CI, 2.0\u20107.3; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), and \u201cPain kept you awake at night\u201d (1.2; 95% CI, 0.4\u20101.9; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01). Similarly, greater deterioration was expected for the SF\u201036v2 Physical Component Summary (8.0; 95% CI, 3.2\u201012.8, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01), Bodily Pain (7.8; 95% CI, 2.0\u201013.5; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01), and Physical Functioning (10.6; 95% CI, 5.5\u201015.6; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Long\u2010term (&gt;3\u2009years) inotersen treatment was associated with slowing and, in some domains, halting of deterioration in key HRQL outcome measures, particularly physical functioning and pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27675","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T05:54:57Z","timestamp":1657259697000},"page":"438-446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>Long\u2010term<\/scp> treatment effects of inotersen on <scp>health\u2010related<\/scp> quality of life in patients with <scp>hATTR<\/scp> amyloidosis with polyneuropathy: Analysis of the <scp>open\u2010label<\/scp> extension of the <scp>NEURO\u2010TTR<\/scp> trial"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3868-2994","authenticated-orcid":false,"given":"Chafic","family":"Karam","sequence":"first","affiliation":[{"name":"Department of Neurology University of Pennsylvania School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Brown","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals\/Akcea Therapeutics, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6517-646X","authenticated-orcid":false,"given":"Nicolae","family":"Done","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Greatsinger","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Bozas","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals\/Akcea Therapeutics, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Vera\u2010Llonch","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals\/Akcea Therapeutics, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Signorovitch","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8708-4"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S219979"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26515"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2012.754348"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-018-0106-z"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-10-S1-O28"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-020-00273-y"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2016.09.518"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-10-S1-P58"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1371"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-1340-x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25257"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns5.12059"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S162913"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00162-z"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716793"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0771-8_6"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14285"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S185677"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-019-00624-w"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-021-00268-x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0210-4"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2005.7.497"},{"key":"e_1_2_12_25_1","volume-title":"User's 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