{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:04:45Z","timestamp":1791428685004,"version":"4.3.3"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","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":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations (<jats:italic>SOD1<\/jats:italic>\u2010ALS). Here we report serious neurologic adverse events (AEs) that occurred in the tofersen clinical trials in people with <jats:italic>SOD1<\/jats:italic>\u2010ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serious neurologic AEs of myelitis, radiculitis, aseptic meningitis, and papilledema reported in the tofersen clinical trials are described. Serious AEs were defined according to International Conference for Harmonization guidelines, and neurologic AEs in clinical trials were diagnosed by investigators based on symptoms, clinical examination findings, and diagnostic workup.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten participants (approximately 7% of tofersen 100\u2010mg\u2013treated trial participants) experienced a total of 12 serious neurologic AEs\u20144 of myelitis, 2 of radiculitis, 2 of aseptic meningitis, and 4 of intracranial hypertension (ICH) and\/or papilledema. All events but one resolved either spontaneously, with dosing interruption\/modification, or with concomitant therapies. One event was ongoing but improved as of December 2022. While 3 events led to tofersen treatment discontinuation, all other participants were able to remain on treatment. No event was life\u2010threatening or fatal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Some antisense oligonucleotides (ASOs) have been described as having pro\u2010inflammatory properties. Aseptic meningitis has been reported with nusinersen; however, myelitis, radiculitis, increased intracranial pressure, and papilledema have not been reported with ASO treatment. These neurologic AEs should be considered when assessing the overall benefit\/risk of tofersen treatment for <jats:italic>SOD1<\/jats:italic>\u2010ALS. Safety data from the open\u2010label extension and expanded access program will continue to characterize these events and further inform the safety profile of tofersen in <jats:italic>SOD1<\/jats:italic>\u2010ALS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28372","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T15:14:02Z","timestamp":1741274042000},"page":"1006-1015","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"71","author":[{"given":"Alexandra","family":"Lovett","sequence":"first","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sowmya","family":"Chary","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suma","family":"Babu","sequence":"additional","affiliation":[{"name":"Sean M. Healey &amp; AMG Center for ALS, Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Bruneteau","sequence":"additional","affiliation":[{"name":"Paris ALS Expert Center and Neurosciences Clinical Research Center, Paris Brain Institute, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Glass","sequence":"additional","affiliation":[{"name":"Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merete","family":"Karlsborg","sequence":"additional","affiliation":[{"name":"Bispebjerg Hospital (M.K.)  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafeeq","family":"Ladha","sequence":"additional","affiliation":[{"name":"Gregory W. Fulton ALS Center Barrow Neurologic Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Mayl","sequence":"additional","affiliation":[{"name":"Maurice Wohl Clinical Neuroscience Institute King's College London  London UK"},{"name":"King's College Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"McDermott","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield UK"},{"name":"NIHR Sheffield Biomedical Research Centre and Clinical Research Facility University of Sheffield  Sheffield UK"},{"name":"Sheffield Teaching Hospitals NHS Foundation Trust  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Bucelli","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Chi\u00f2","sequence":"additional","affiliation":[{"name":"Rita Levi Montalcini Department of Neuroscience University of Turin  Turin Italy"},{"name":"Azienda Ospedaliero\u2010Universitaria Citt\u00e0 Della Salute e Della Scienza of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby A.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thos","family":"Cochrane","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Fradette","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Smirnakis","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Inra","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohail","family":"Malek","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fanning","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858414561795"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200908164"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt097"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm110"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03555.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99081"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25424"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2003715"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"e_1_2_11_11_1","unstructured":"ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting."},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1144-2"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2021.11.007"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28359"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623314551840"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12251"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.136"},{"key":"e_1_2_11_18_1","unstructured":"European Medicines Agency Scientific Conclusions and Grounds for the Variation to the Terms of the Marketing Authorisation(s)."},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27042"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12442-w"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30394-6"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000244"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.01.002"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.890958"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a6cc13"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1604761"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000025580"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1941874418783914"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010023\u201012130\u20101"},{"key":"e_1_2_11_30_1","unstructured":"S.Malek A.Lovett T.Cochrane et\u00a0al. \u201cTofersen Safety Experience From an Ongoing Global Early Access Program \u201d2023Barcelona Spain."}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.28372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T12:04:55Z","timestamp":1746705895000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.28372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/mus.28372"],"URL":"https:\/\/doi.org\/10.1002\/mus.28372","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]},"assertion":[{"value":"2024-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}