{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T08:06:17Z","timestamp":1773648377341,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>While randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of therapies in amyotrophic lateral sclerosis (ALS), post hoc analyses can provide critical insights into clinical effectiveness, treatment durability, and subpopulation responses. Several post hoc analyses of Study MCI186\u201019 (Study 19), the pivotal phase 3 RCT that supported the United States Food and Drug Administration approval of intravenous edaravone, have been performed to explore the broader clinical impact of this therapy. These analyses assessed the long\u2010term treatment efficacy, changes in individual ALS Functional Rating Scale\u2013Revised item scores, survival and additional milestone events, and the impact of edaravone in patient subgroups defined by disease progression trajectories using latent class analysis. Collectively, these findings reinforce the long\u2010term clinical benefit of edaravone and demonstrate that edaravone may offer benefits across a spectrum of ALS disease trajectories, beyond those defined in the original study criteria. These studies help address questions not captured in the original RCT and may inform future trial design and treatment decisions.<\/jats:p>","DOI":"10.1002\/mus.70039","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:29:44Z","timestamp":1770460184000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study 19 (\n                    <scp>MCI186<\/scp>\n                    \u201019) Post Hoc Analyses"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1914-5061","authenticated-orcid":false,"given":"Benjamin Rix","family":"Brooks","sequence":"first","affiliation":[{"name":"Clinical Trials Planning LLC  Charlotte North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Shefner","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute  Phoenix Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-3953","authenticated-orcid":false,"given":"Stephen","family":"Apple","sequence":"additional","affiliation":[{"name":"Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30115-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1364269"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-022-00391-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1645858"},{"key":"e_1_2_8_6_1","unstructured":"A.DmitrienkoandI.Lipkovich Exploratory Subgroup Analysis: Post\u2010Hoc Subgroup Identification in Clinical Trials.EMA Expert Workshop(2014)."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2014.959024"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1599955"},{"issue":"9","key":"e_1_2_8_9_1","first-page":"S175","article-title":"Edaravone in the Treatment of Amyotrophic Lateral Sclerosis: Efficacy and Access to Therapy\u2014A Roundtable Discussion","volume":"24","author":"Brooks B. R.","year":"2018","journal-title":"American Journal of Managed Care"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1353101"},{"issue":"1","key":"e_1_2_8_11_1","first-page":"47","article-title":"Edaravone in Amyotrophic Lateral Sclerosis\u2014Lessons From the Clinical Development Program and the Importance of a Strategic Clinical Trial Design","volume":"14","author":"Beydoun S. R.","year":"2018","journal-title":"US Neurology"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1361446"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26740"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27467"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27946"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2024.123290"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1365372"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26042"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2016.1140786"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5609-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1044\/2018_JSLHR-S-17-0366"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26875"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2016-314661"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2022.2153607"}],"updated-by":[{"DOI":"10.1002\/mus.70195","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000}}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70039","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.70039","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T05:49:03Z","timestamp":1771220943000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":23,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/mus.70039"],"URL":"https:\/\/doi.org\/10.1002\/mus.70039","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}