{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:14:09Z","timestamp":1790421249190,"version":"4.1.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"13","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Neurofilament light chain (NfL) is a promising marker for predicting disease activity in relapsing multiple sclerosis (RMS). To date, however, there has been no commercially available NfL assay validated in MS and intended for routine clinical use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      To identify and validate a single threshold for NfL in blood that differentiates RMS patients, aged 18\u201355\u2009years, at a higher versus lower risk of disease activity over 2\u2009years, using the Atellica\n                      <jats:sup>\u00ae<\/jats:sup>\n                      IM NfL assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The optimal NfL threshold for this assay\/use case was identified and independently validated using ASCLEPIOS I and II data, respectively. The primary endpoint (annualized number of new\/enlarging T2 (neT2) lesions) was analyzed using negative binomial models. Threshold optimization used maximum likelihood methodology. Generalizability analyses used data from ASCLEPIOS II, FREEDOMS, and TRANSFORMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>NfL concentration of 12.9\u2009pg\/mL was validated as the optimal cutoff for prognosticating disease activity as measured by neT2 lesion over 2\u2009years. This threshold prognosticated individual patient risk for persistent disease activity (&gt;3 neT2 lesions\/year over 2\u2009years) and showed prognostic value across relevant subgroups and clinical scenarios. Findings for relapses were similar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The CE-marked Atellica\n                      <jats:sup>\u00ae<\/jats:sup>\n                      IM NfL assay is now validated for prognostic use in RMS patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251389797","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T11:14:54Z","timestamp":1761736494000},"page":"1543-1556","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Clinical validation of a novel in vitro diagnostic neurofilament light chain assay for the prognostication of disease activity in people with relapsing multiple sclerosis"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-8202","authenticated-orcid":false,"given":"Tjalf","family":"Ziemssen","sequence":"first","affiliation":[{"name":"Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), University of Ottawa; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-0335","authenticated-orcid":false,"given":"Amit","family":"Bar-Or","sequence":"additional","affiliation":[{"name":"Center for Neuroinflammation and Experimental Therapeutics, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-9918","authenticated-orcid":false,"given":"Xavier","family":"Montalban","sequence":"additional","affiliation":[{"name":"Department of Neurology-Neuroimmunology, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Hospital Universitari Vall d\u2019Hebron, Universitat Autonoma de Barcelona (UAB), Barcelona, Spain; Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-0837","authenticated-orcid":false,"given":"Charlotte E","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5690-8710","authenticated-orcid":false,"given":"Dieter A","family":"H\u00e4ring","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Kukkaro","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Merschhemke","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd C","family":"Kieseier","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-7837","authenticated-orcid":false,"given":"Meghana","family":"Karnik-Henry","sequence":"additional","affiliation":[{"name":"Siemens Healthineers, Tarrytown, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Gee","sequence":"additional","affiliation":[{"name":"Siemens Healthineers, Tarrytown, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Lange","sequence":"additional","affiliation":[{"name":"Siemens Healthineers, Tarrytown, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddine","family":"Merabet","sequence":"additional","affiliation":[{"name":"Siemens Healthineers, Tarrytown, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-4422","authenticated-orcid":false,"given":"Tanuja","family":"Chitnis","sequence":"additional","affiliation":[{"name":"Harvard Medical School; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women\u2019s Hospital; Brigham Multiple Sclerosis Center, Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2179-3655","authenticated-orcid":false,"given":"Stefan","family":"Bittner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Focus Program Translational Neuroscience and Immunology, Rhine Main Neuroscience Network, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Wiendl","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Neurologie und Neurophysiologie, Universit\u00e4tsklinikum Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4932-4001","authenticated-orcid":false,"given":"Stephen L","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520988637"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30067-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac016"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0170-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000622"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517751049"},{"key":"e_1_3_3_8_2","article-title":"Brain health: Time matters in multiple sclerosis","volume":"1","author":"Giovannoni G","year":"2016","unstructured":"Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: Time matters in multiple sclerosis. Mult Scler Relat Disord 2016; 9 suppl 1: S5\u2013S48.","journal-title":"Mult Scler Relat Disord"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-00955-x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518765666"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320106"},{"key":"e_1_3_3_12_2","unstructured":"CMSC. CMSC best practices for the use of serum neurofilament (sNfL) in MS management https:\/\/www.mscare.org\/best-practices-guideline-on-the-use-of-neurofilament\/ (2024 accessed June 2024)."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585241277044"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1571605"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm15020069"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab241"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.104970"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-022-00427-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007032"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.852563"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24954"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.103535"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00009-6"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy154"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.638"},{"key":"e_1_3_3_26_2","unstructured":"Siemens Healthineers. Neurofilament light chain blood test for multiple sclerosis developed by Siemens Healthineers is first of its kind to achieve CE mark https:\/\/www.siemens-healthineers.com\/press\/releases\/neurofilament-light-chain-multiple-sclerosis (2024 Accessed January 2025)."},{"key":"e_1_3_3_27_2","volume-title":"Atellica IM Neurofilament Light Chain (NfL) Assay Instructions for Use [Package Insert]","author":"Siemens Healthineers","year":"2024","unstructured":"Siemens Healthineers. Atellica IM Neurofilament Light Chain (NfL) Assay Instructions for Use [Package Insert]. Tarrytown, NY: Siemens Healthineers, 2024."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1917246"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909494"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907839"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005347"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51060"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00095-8"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.654942"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.693017"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.2217\/cer-2020-0267"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.57264\/cer-2023-0016"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251389797","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585251389797","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251389797","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:19:43Z","timestamp":1777695583000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585251389797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":36,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1177\/13524585251389797"],"URL":"https:\/\/doi.org\/10.1177\/13524585251389797","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}