{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:45:59Z","timestamp":1787237159109,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Elezanumab is a monoclonal antibody that binds repulsive guidance molecule a (RGMa), an inhibitor of central nervous system regeneration after inflammation or injury. The aim was to assess the safety and efficacy of elezanumab in relapsing and progressive forms of multiple sclerosis (MS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RADIUS\u2010R and RADIUS\u2010P were phase 2 trials in relapsing (RADIUS\u2010R) or progressive (RADIUS\u2010P) MS. Participants were randomized to intravenous elezanumab 400mg, 1800mg, or placebo every 4\u2009weeks through week 48. The primary endpoint was the mean Overall Response Score (ORS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In RADIUS\u2010R, 208 participants received elezanumab 400mg (n\u2009=\u200969), elezanumab 1800mg (n\u2009=\u200969), or placebo (n\u2009=\u200970). In RADIUS\u2010P, 123 participants received elezanumab 400mg (n\u2009=\u200940), elezanumab 1800mg (n\u2009=\u200940), or placebo (n\u2009=\u200943). The primary endpoint of ORS was not met in either study. For RADIUS\u2010R, mean ORS was \u22120.2 with effect size of \u22120.2 for elezanumab 400mg and\u2009\u22120.2 with effect size of \u22120.2 for elezanumab 1800mg. For RADIUS\u2010P, mean ORS was 0.0 with effect size of 0.0 for elezanumab 400mg and 0.1 with effect size of 0.1 for elezanumab 1800mg.<\/jats:p>\n                    <jats:p>Elezanumab was well tolerated; the rate of serious adverse events was similar across treatment groups in both studies. Adverse events with \u226510% of elezanumab population were falls, urinary tract infections, headaches in RADIUS\u2010R and RADIUS\u2010P, and also fatigue, infusion\u2010related reactions, and muscular weakness in RADIUS\u2010P.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Elezanumab was safe and well tolerated, but did not meet the primary endpoint in either study. ANN NEUROL 2025;98:590\u2013602<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27262","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T13:32:41Z","timestamp":1753277561000},"page":"590-602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Randomized, Double\u2010Blind, Placebo\u2010Controlled, Multiple\u2010Dose Studies to Assess the Safety and Efficacy of Elezanumab when Added to Standard of Care in Relapsing and Progressive Forms of Multiple Sclerosis"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-2533","authenticated-orcid":false,"given":"Bruce A.C.","family":"Cree","sequence":"first","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ottawa Hospital Research Institute University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gold","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  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Presented at the 2020 International Society for CNS Clinical Trials and Methodology (ISCTM) annual meeting Washington DC USA February 21\u201325 2020 Available at:https:\/\/isctm.org\/public_access\/Feb2020\/Posters\/Villalta-Gil-Poster.pdf."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30137-1"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516638941"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00179-4"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32346-2"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30347-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008519"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.27262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T08:29:20Z","timestamp":1756369760000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.27262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/ana.27262"],"URL":"https:\/\/doi.org\/10.1002\/ana.27262","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]},"assertion":[{"value":"2024-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}