{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:01:59Z","timestamp":1785859319357,"version":"3.56.0"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Intravenous (IV) edaravone is a US Food and Drug Administration\u2013approved treatment for amyotrophic lateral sclerosis (ALS), shown in clinical trials to slow physical functional decline. In this study we compared the effect of IV edaravone (edaravone\u2010first group) versus placebo followed by IV edaravone (placebo\u2010first group) on survival and additional milestone events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This work is a post hoc analysis of Study 19\/MCI186\u201019, which was a randomized, placebo\u2010controlled, phase 3 study investigating IV edaravone versus placebo. Study 19 and its 24\u2010week extension have been described previously (NCT01492686). Edaravone\u2010first versus placebo\u2010first group time to events for specific milestone(s) were analyzed post hoc. Time\u2010to\u2010event composite endpoints were time to death; time to death, tracheostomy, or permanent assisted ventilation (PAV); and time to death, tracheostomy, PAV, or hospitalization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The risk for death, tracheostomy, PAV, or hospitalization was 53% lower among patients in the edaravone\u2010first vs placebo\u2010first groups (hazard ratio\u2009=\u20090.47 [95% confidence interval 0.25 to 0.88], <jats:italic>P<\/jats:italic>\u2009=\u2009.02). The overall effect of IV edaravone on ALS progression could be seen in the significant separation of time\u2010to\u2010event curves for time to death, tracheostomy, PAV, or hospitalization. ALS survival composite endpoint analyses (ALS\/SURV) suggested a treatment benefit (least\u2010squares mean difference) for the edaravone\u2010first versus the placebo\u2010first group at week 24 (0.15\u2009\u00b1\u20090.05 [95% confidence interval 0.06 to 0.25], <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01) and week 48 (0.11\u2009\u00b1\u20090.05 [95% confidence interval 0.02 to 0.21], <jats:italic>P<\/jats:italic>\u2009=\u2009.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These analyses illustrate the value of timely and continued IV edaravone treatment, as earlier initiation was associated with a lower risk of death, tracheostomy, PAV, or hospitalization in patients with ALS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27946","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T06:54:10Z","timestamp":1690872850000},"page":"397-403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"68","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"},{"name":"Atrium Health Neuroscience Institute, Neuromuscular\/ALS\u2010MDA Care Center and ALSA Center of Excellence, Department of Neurology, Carolinas Medical Center University of North Carolina School of Medicine\u2014Charlotte Campus  Charlotte North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0737-6065","authenticated-orcid":false,"given":"Erik P.","family":"Pioro","sequence":"additional","affiliation":[{"name":"Neuromuscular Division, Davee Department of Neurology Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Sakata","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-5332","authenticated-orcid":false,"given":"Fumihiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Hagan","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-3953","authenticated-orcid":false,"given":"Stephen","family":"Apple","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1603471"},{"key":"e_1_2_11_3_1","unstructured":"Rilutek\u00ae (riluzole). Prescribing information.Covis Pharmaceuticals Inc.;2016."},{"key":"e_1_2_11_4_1","article-title":"Prescribing information","author":"Radicava\u00ae (edaravone)","year":"2022","journal-title":"Mitsubishi Tanabe Pharma Corporation"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181bc01a4"},{"issue":"9","key":"e_1_2_11_6_1","first-page":"S175","article-title":"Edaravone in the treatment of amyotrophic lateral sclerosis: efficacy and access to therapy\u2010a roundtable discussion","volume":"24","author":"Brooks BR","year":"2018","journal-title":"Am J Manag Care."},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(17)30115\u20101"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1364269"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1365372"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26740"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1317812"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010020\u201004254\u2010w"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1643375"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101590"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2022.10.011"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016357.2017.1420228"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102019\u2010322213"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000518908"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1361445"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1353100"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27946","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T10:27:27Z","timestamp":1706178447000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.27946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/mus.27946"],"URL":"https:\/\/doi.org\/10.1002\/mus.27946","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,31]]},"assertion":[{"value":"2022-11-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}