{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T02:03:30Z","timestamp":1780538610522,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>On\/Off dosing of intravenous (IV) edaravone and edaravone oral suspension was US Food and Drug Administration (FDA)\u2010approved for Amyotrophic Lateral Sclerosis (ALS) treatment. Placebo\u2010controlled trials showed that IV edaravone slows the rate of physical functional decline in patients with ALS. Here, the impact of edaravone oral suspension on function and survival was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Edaravone oral suspension was investigated in clinical trials MT\u20101186\u2010A01\/A02\/A03\/A04. Patients from Studies MT\u20101186\u2010A02\/A04 (prespecified analysis) and Studies MT\u20101186\u2010A01\/A02\/A03\/A04 (post hoc analysis) were propensity score matched 1:1 on 10 baseline variables with historical Pooled Resource Open\u2010Access ALS Clinical Trials (PRO\u2010ACT) placebo patients (not receiving active investigational treatment in their trials) to assess the impact of edaravone oral suspension on function and survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the prespecified analysis, 78 edaravone oral suspension\u2013treated patients from Studies MT\u20101186\u2010A02\/A04 demonstrated a survival benefit versus 78 matched PRO\u2010ACT placebo patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.005). Baseline risk\u2010adjusted hazard ratio showed an 84% decreased risk of death in edaravone oral suspension versus PRO\u2010ACT placebo patients (<jats:italic>p\u2009=<\/jats:italic>\u20090.005). ALS Functional Rating Scale\u2010Revised (ALSFRS\u2010R) total score change from baseline at Week 48 was \u22128.4 points for edaravone oral suspension versus \u221214.1 points for PRO\u2010ACT placebo patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In the post hoc analysis, patients from Studies MT\u20101186\u2010A01\/A02\/A03\/A04 (<jats:italic>n<\/jats:italic>\u2009=\u2009210) propensity score matched to PRO\u2010ACT placebo patients (<jats:italic>n<\/jats:italic>\u2009=\u2009210) showed statistically significantly longer time to death and smaller ALSFRS\u2010R change from baseline at Week 48; restricted mean survival time showed a 7.3\u2010month improvement (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This suggests edaravone oral suspension significantly increases survival time and decreases physical functional decline versus PRO\u2010ACT placebo patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28462","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:58:49Z","timestamp":1751353129000},"page":"586-596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Analysis of Long\u2010Term Function and Survival of Edaravone Oral Suspension\u2013Treated Patients With Amyotrophic Lateral Sclerosis Using <scp>PRO<\/scp>\u2010<scp>ACT<\/scp> Data as Historical Placebo Controls"],"prefix":"10.1002","volume":"72","author":[{"given":"Fumihiro","family":"Takahashi","sequence":"first","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Genge","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute and Hospital  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Hirai","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Selness","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Todorovic","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Europe, Ltd.  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Art","family":"Wamil","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nissim","family":"Sasson","sequence":"additional","affiliation":[{"name":"NStat Solutions Biostatistical Services  Rehovot Israel"}],"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"}]},{"given":"Yoshiteru","family":"Ushirogawa","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Pooled Resource Open\u2010Access ALS Clinical Trials Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Prescribing Information","author":"Radicava (Edaravone) IV and Radicava ORS (Edaravone) Oral Suspension","year":"2022"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30115-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.925"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.952"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27768"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2021.1927102"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26740"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1364269"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1365372"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27946"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101590"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000951"},{"key":"e_1_2_11_14_1","unstructured":"PRO\u2010ACT \u201cThe ALS Association & Neurological Clinical Research Institute \u201dhttps:\/\/ncri1.partners.org\/proact."},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.28448"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.28451"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000194316.91908.8a"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.433"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2307\/2683903"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51915"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3697"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.2208"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.14645"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09993-z"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.4893"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/17482960903093710"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2021.2004167"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.8.1139"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3109\/17482968.2011.593037"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/14660820500396984"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2013.763281"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(76)90044-8"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-1332-x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30089-9"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.28462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T13:46:15Z","timestamp":1757943975000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.28462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/mus.28462"],"URL":"https:\/\/doi.org\/10.1002\/mus.28462","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2024-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}