{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:32:28Z","timestamp":1754487148096,"version":"3.40.5"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"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":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv\u2010PN) is a genetic condition associated with significant morbidity and mortality. In this study we aimed to identify patient subgroups exhibiting the greatest health\u2010related quality of life (HRQL) benefit from inotersen treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined data from the inotersen phase 2\/3 randomized, controlled trial for ATTRv\u2010PN, NEURO\u2010TTR (NCT01737398, 66\u2009weeks). LASSO regression models predicted changes in Norfolk QoL\u2010DN total score (TQoL, range\u2009\u22124 to 136; higher scores indicate poorer HRQL) from baseline in the inotersen and placebo arm, respectively. Individualized efficacy scores (ES) were calculated as differences between predicted change scores had patients received inotersen vs placebo. Patients were ranked by ES to define the greatest\u2010benefit subpopulation (top 50%). Characteristics of the top 50% and bottom 50% of patients were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The overall mean\u2009\u00b1\u2009standard deviation TQoL change was \u22120.20\u2009\u00b1\u200919.13 for inotersen (indicating no change) and 10.77\u2009\u00b1\u200921.13 for placebo (indicating deterioration). Within the highest\u2010benefit patients, mean TQoL change was \u221211.03\u2009\u00b1\u200917.06 (improvement) for inotersen and 11.24\u2009\u00b1\u200922.97 (deterioration) for placebo (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). Compared with the overall population, patients in the greatest\u2010benefit subpopulation were younger, more likely to have polyneuropathy disability (PND) scores 1 or 2, less likely to have received prior tafamidis or diflunisal treatment, and more likely to have Val30Met mutations and higher (worse) baseline TQoL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients who were younger and\/or at earlier polyneuropathy stages experienced greater HRQL benefits from inotersen over 66\u2009weeks. These findings underscore the need for early diagnosis and treatment initiation, especially among more severely affected patients in early stages of ATTRv\u2010PN.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27668","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T10:19:31Z","timestamp":1656497971000},"page":"319-328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Factors associated with increased <scp>health\u2010related<\/scp> quality\u2010of\u2010life benefits in hereditary transthyretin amyloidosis polyneuropathy patients treated with inotersen"],"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  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan","family":"Brown","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals\/Akcea Therapeutics, Inc  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibou","family":"Dieye","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Bozas","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals\/Akcea Therapeutics, Inc  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Vera Llonch","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals\/Akcea Therapeutics, Inc  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Signorovitch","sequence":"additional","affiliation":[{"name":"Analysis Group, Inc  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_11_2_1","DOI":"10.1007\/s00415-017-8708-4"},{"doi-asserted-by":"publisher","key":"e_1_2_11_3_1","DOI":"10.2147\/TCRM.S219979"},{"doi-asserted-by":"publisher","key":"e_1_2_11_4_1","DOI":"10.1016\/S1474-4422(11)70246-0"},{"doi-asserted-by":"publisher","key":"e_1_2_11_5_1","DOI":"10.1111\/j.1749-6632.1984.tb13742.x"},{"doi-asserted-by":"publisher","key":"e_1_2_11_6_1","DOI":"10.1186\/1750-1172-8-31"},{"doi-asserted-by":"publisher","key":"e_1_2_11_7_1","DOI":"10.1007\/s00415-019-09688-0"},{"doi-asserted-by":"publisher","key":"e_1_2_11_8_1","DOI":"10.1002\/humu.22619"},{"doi-asserted-by":"publisher","key":"e_1_2_11_9_1","DOI":"10.1007\/s40120-018-0106-z"},{"doi-asserted-by":"publisher","key":"e_1_2_11_10_1","DOI":"10.1186\/1750-1172-10-S1-O28"},{"doi-asserted-by":"publisher","key":"e_1_2_11_11_1","DOI":"10.1186\/s13023-020-1340-x"},{"doi-asserted-by":"publisher","key":"e_1_2_11_12_1","DOI":"10.2217\/nmt-2019-0020"},{"doi-asserted-by":"publisher","key":"e_1_2_11_13_1","DOI":"10.1002\/mus.25257"},{"doi-asserted-by":"publisher","key":"e_1_2_11_14_1","DOI":"10.1111\/jns5.12059"},{"doi-asserted-by":"publisher","key":"e_1_2_11_15_1","DOI":"10.1056\/NEJMoa1716793"},{"doi-asserted-by":"publisher","key":"e_1_2_11_16_1","DOI":"10.1212\/WNL.0b013e3182661eb1"},{"doi-asserted-by":"publisher","key":"e_1_2_11_17_1","DOI":"10.1056\/NEJMoa1716153"},{"doi-asserted-by":"publisher","key":"e_1_2_11_18_1","DOI":"10.1002\/lt.24058"},{"doi-asserted-by":"publisher","key":"e_1_2_11_19_1","DOI":"10.1097\/TP.0000000000000574"},{"doi-asserted-by":"publisher","key":"e_1_2_11_20_1","DOI":"10.1212\/WNL.0b013e3181ea15d4"},{"doi-asserted-by":"publisher","key":"e_1_2_11_21_1","DOI":"10.1038\/s41582-019-0210-4"},{"doi-asserted-by":"publisher","key":"e_1_2_11_22_1","DOI":"10.2147\/DDDT.S162913"},{"unstructured":"US Food and Drug Administration.TEGSEDI (inotersen)\u2014Prescribing Information.2022. 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