{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:41:51Z","timestamp":1788615711916,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"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":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>The degree of change in neuropathic impairment and quality of life (QoL) that is clinically meaningful to patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv\u2010PN) is not established. This study aimed to estimate the magnitude of treatment differences that are meaningful to patients in measures of neuropathy and QoL and to determine whether eplontersen achieved a meaningful improvement versus placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from the NEURO\u2010TTRansform trial on patients with ATTRv\u2010PN treated with eplontersen (<jats:italic>n<\/jats:italic>\u2009=\u2009141) or historical placebo (<jats:italic>n<\/jats:italic>\u2009=\u200959) were used. Anchor\u2010based approaches were used to estimate thresholds for meaningful differences in the modified Neuropathy Impairment Score +7 (mNIS+7) composite score, Norfolk QoL\u2010Diabetic Neuropathy (Norfolk QoL\u2010DN) total score, Neuropathy Symptoms and Change (NSC) total score, and modified body mass index (mBMI). Differences between the least squares means of the treatment groups were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Meaningful improvement in mNIS+7 was estimated as \u22124.0 points and deterioration as 1.8 points. The estimated ranges of meaningful improvement and deterioration in Norfolk QoL\u2010DN were \u221212.8 to \u22124.0 points, and 5.9 to 14.7 points, respectively. For NSC, ranges were \u22122.4 to \u22121.3 points for meaningful improvement, and 0.6 to 5.8 points for deterioration. The estimated meaningful improvement in mBMI was 9.8\u2009kg\/m<jats:sup>2<\/jats:sup>\u2009\u00d7 g\/L and deterioration was \u221240.9\u2009kg\/m<jats:sup>2<\/jats:sup>\u2009\u00d7 g\/L. Improvements in each measure with eplontersen versus placebo were greater than the estimates of meaningful differences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Eplontersen demonstrated a clinically meaningful effect on neuropathic impairment, QoL, and nutritional status. Such estimates have implications for clinical practice and trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28299","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T06:48:52Z","timestamp":1731912532000},"page":"96-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Estimating Meaningful Differences in Measures of Neuropathic Impairment, Health\u2010Related Quality of Life, and Nutritional Status in Patients With Hereditary Transthyretin Amyloidosis"],"prefix":"10.1002","volume":"71","author":[{"given":"Folke","family":"Folkvaljon","sequence":"first","affiliation":[{"name":"HTA Statistics &amp; Data Science, BioPharmaceuticals Medical AstraZeneca  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morie","family":"Gertz","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian D.","family":"Gillmore","sequence":"additional","affiliation":[{"name":"National Amyloidosis Centre University College London, Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Khella","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Masri","sequence":"additional","affiliation":[{"name":"OHSU Center for Hypertrophic Cardiomyopathy and Amyloidosis  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew S.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia Waddington","family":"Cruz","sequence":"additional","affiliation":[{"name":"CEPARM, Amyloidosis Center, University Hospital Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Wixner","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jersey","family":"Chen","sequence":"additional","affiliation":[{"name":"Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&amp;D AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Reicher","sequence":"additional","affiliation":[{"name":"Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&amp;D AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Kwoh","sequence":"additional","affiliation":[{"name":"Ionis  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Yarlas","sequence":"additional","affiliation":[{"name":"Ionis  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1768-2373","authenticated-orcid":false,"given":"John L.","family":"Berk","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01960-9"},{"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":"10.1080\/13506129.2022.2091985"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716793"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.18688"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716153"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2019.116424"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2005.7.497"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27023"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-31"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-023-03116-7"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1994.tb01106.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-021-00235-6"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-022-00414-z"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns5.12059"},{"key":"e_1_2_12_17_1","volume-title":"Patient\u2010Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision\u2010Making","author":"FDA","year":"2023"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.03.012"},{"key":"e_1_2_12_19_1","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen J.","year":"1998"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10635-1"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.28299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T15:32:52Z","timestamp":1733931172000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.28299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,17]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/mus.28299"],"URL":"https:\/\/doi.org\/10.1002\/mus.28299","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,17]]},"assertion":[{"value":"2024-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}