{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:20:40Z","timestamp":1789568440143,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012351","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":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/aims<\/jats:title><jats:p>Edaravone in amyotrophic lateral sclerosis (ALS) was analyzed in two phase 3 studies (MCI186\u201016 and MCI186\u201019). Those trials enrolled patients with Japanese ALS severity grades 1 and 2 (less severe ALS), but many patients progressed to grades 3 and 4 during the double\u2010blind treatment period. The placebo patients who initiated edaravone treatment in the open\u2010label periods provided an opportunity to assess the effects of edaravone in more severe ALS. This study also assessed the association between ALS Functional Rating Scale\u2010Revised (ALSFRS\u2010R) slope and biomarker changes after open\u2010label edaravone initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Change in ALSFRS\u2010R slope in placebo patients before and after initiating edaravone treatment was assessed using the random coefficient model. The association of ALSFRS\u2010R change and blood marker changes was explored by the least absolute shrinkage and selection operator (LASSO) method of machine learning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four percent of patients (35\/146) in the placebo\u2010edaravone group showed \u226525% slowing of decline in the ALSFRS\u2010R slope. Within the 25% slower\u2010decline group, 60% (21\/35) had Japanese ALS severity grades 3 or 4 at the start of edaravone treatment. The LASSO model identified serum urate as associated with the percentage change in ALSFRS\u2010R slope. The rate of decrease in urate was smaller in the 25% slower\u2010decline group than in the non\u201025% slower\u2010decline group during edaravone treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This post hoc analysis indicated that ALS patients, including those with advanced ALS severity grades, may receive benefit in the group of patients whose urate levels are stable during the course of the edaravone treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27699","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T17:20:35Z","timestamp":1660238435000},"page":"583-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Associations between urate levels and amyotrophic lateral sclerosis functional score with edaravone treatment: Post hoc analysis of studies <scp>MCI186<\/scp>\u201016, <scp>MCI186<\/scp>\u201017, and <scp>MCI186<\/scp>\u201019"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-5332","authenticated-orcid":false,"given":"Fumihiro","family":"Takahashi","sequence":"first","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kano","sequence":"additional","affiliation":[{"name":"Department of Neurology Toho University Faculty of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Nagano","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatomo","family":"Yoneoka","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Nelson","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiteru","family":"Ushirogawa","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2014.959024"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1362000"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1363780"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1599955"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30115-1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-8467(03)00031-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18627-w"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.6179"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04706-5"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14409"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.10.1757"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.51.7465"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.1129"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51299"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2020.1746810"},{"key":"e_1_2_11_17_1","unstructured":"Amyotrophic lateral sclerosis (ALS) (designated intractable disease 2).Japan intractable disease information center.https:\/\/www.nanbyou.or.jp\/wp-content\/uploads\/upload_files\/File\/002-201704-kijyun.pdf(Japanese). Accessed July 21 2022."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1364269"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/146608200300079536"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/17482960903093710"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2022.2051964"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1361441"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5735-9"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-014-7331-x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25950"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6440-7"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19609-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2015.11.4.376"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2021.106566"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.06.002"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-015-0604-7"},{"issue":"3","key":"e_1_2_11_32_1","first-page":"104","article-title":"Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration","volume":"21","author":"Nagase M","year":"2016","journal-title":"Redox Rep"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.16-63"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.671"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02870707"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5609-1"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2016.1140786"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26042"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27699","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.27699","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27699","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T06:52:47Z","timestamp":1692514367000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.27699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":37,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/mus.27699"],"URL":"https:\/\/doi.org\/10.1002\/mus.27699","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]},"assertion":[{"value":"2021-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}