{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:32:46Z","timestamp":1764333166619,"version":"3.40.5"},"reference-count":19,"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"}]}],"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>In this study we examined the relationship between urate levels at baseline and functional change measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale\u2014Revised (ALSFRS\u2010R) total score after edaravone treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from the edaravone trials MCI186\u201016, MCI186\u201017, and MCI186\u201019 were analyzed, including the following treatment sequence groups: edaravone\u2010edaravone (EE, n\u00a0=\u00a0113); edaravone\u2010placebo (EP, n\u00a0=\u00a045); and placebo\u2010edaravone (PE, n\u00a0=\u00a0146). Subgroups were defined as low baseline urate (below the median value of 4.8\u00a0mg\/dL) and high baseline urate (\u22654.8\u00a0mg\/dL). The differences in ALSFRS\u2010R total score change and urate change were evaluated using the mixed model for repeated measurement for overall population, by urate\u2010level subgroup, and by trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the PE group, the EE group showed a slower decline in ALSFRS\u2010R score, regardless of the urate baseline level, and a slower decline in urate level in the higher baseline urate subgroup. Smaller changes in ALSFRS\u2010R score and urate were observed in patients diagnosed with \u201cprobable, laboratory\u2010supported ALS.\u201d There was a positive correlation between changes from baseline to cycle 12 in urate levels and ALSFRS\u2010R score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Edaravone treatment in ALS patients diagnosed with \u201cdefinite ALS\u201d or \u201cprobable ALS\u201d showed slowing of disease progression, regardless of baseline urate level. In addition, because edaravone treatment was associated with a slower decline in urate level in the higher baseline urate subgroup and urate\u2010level changes were associated with changes in ALSFRS\u2010R score, urate level, and\/or change may be one indicator in predicting disease progression after edaravone administration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27700","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T13:03:19Z","timestamp":1660222999000},"page":"593-602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Associations between the <scp>ALSFRS\u2010R<\/scp> score and urate levels during 12\u2009months of edaravone treatment for amyotrophic lateral sclerosis: Post hoc analysis of <scp>ALSFRS\u2010R<\/scp> scores in clinical 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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Kano","sequence":"additional","affiliation":[{"name":"Department of Neurology Toho University, Faculty of Medicine  Ota\u2010ku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshito","family":"Nagano","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takatomo","family":"Yoneoka","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Nelson","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc  Jersey City New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiteru","family":"Ushirogawa","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"e_1_2_11_2_1","article-title":"Associations between urate levels and amyotrophic lateral sclerosis functional score with edaravone treatment: post hoc analysis of studies MCI186\u201016, MCI186\u201017, and MCI186\u201019","author":"Takahashi F","year":"2022","journal-title":"Muscle Nerve"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2022.2051964"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.6858"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.06.002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000027524.86752.02"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5735-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20472"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25950"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6440-7"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2015.11.4.376"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000488038"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2014.959024"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1362000"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30115-1"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2016.1214733"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.10.94"},{"key":"e_1_2_11_18_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. 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