{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:14:58Z","timestamp":1793218498722,"version":"4.5.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/Objectives:<\/jats:title>\n                    <jats:p>Neurofilament light chain (NfL) is a promising biomarker for monitoring disease activity and treatment response in multiple sclerosis (MS). This meta-regression assesses the relationship between treatment effects on serum\/plasma NfL (s\/pNfL) and clinical and radiological endpoints in randomized controlled trials (RCTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A systematic PubMed search identified RCTs in MS (1999\u20132023) with \u2a7e24\u2009months\u2019 duration and s\/pNfL data. Extracted outcomes included treatment effects on s\/pNfL, annualized relapse rate (ARR), confirmed disability worsening (CDW), magnetic resonance imaging (MRI) new\/enlarging T2 lesions, and percentage brain volume change (PBVC). We evaluated the association of treatment effect on the selected outcomes at the trial level by a meta-regression, weighted by trial size and duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Fifteen RCTs (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20096814) were included, nine in relapsing MS (RMS,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20095221), and six in progressive MS (PMS,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20091593). Treatment effects on s\/pNfL showed a moderate association with treatment effects on MRI new\/enlarging T2 lesions (\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.42,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.01), ARR (\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u20090.33,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.03) and CDW (\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u20090.30,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.04), but not with PBVC. In RMS-only trials, association with ARR (\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u20090.45,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.05) and CDW (\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u20090.50, p\u2009=\u20090.03) was more pronounced.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In MS, treatment effects on s\/pNfL are moderately associated with therapeutic effects on ARR, MRI new\/enlarging T2 lesions, and CDW, whereas no consistent association was observed with PBVC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251407973","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:03:33Z","timestamp":1769162613000},"page":"268-278","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Neurofilament light chain as a surrogate candidate for disease activity in multiple sclerosis (LUMINOUS)\u2014A meta-regression of randomized controlled trials"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4129-1276","authenticated-orcid":false,"given":"Roxanne","family":"Pretzsch","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Centre, Departments of Neurology, Clinical Research and Biomedicine, University Hospital Basel and University of Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Switzerland; Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2737-8305","authenticated-orcid":false,"given":"Sahla","family":"El Mahdaoui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Copenhagen University Hospital Danish Multiple Sclerosis Research Center, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4153-428X","authenticated-orcid":false,"given":"Poljanka","family":"Johnson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7508-0645","authenticated-orcid":false,"given":"Mafalda Delgado","family":"Soares","sequence":"additional","affiliation":[{"name":"S\u00e3o Jos\u00e9 Local Health Unit, Neurology and Multiple Sclerosis Centre of Integrated Responsibility, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7081-3096","authenticated-orcid":false,"given":"Kimberly","family":"Koerbel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Goethe-University, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Held","sequence":"additional","affiliation":[{"name":"Department of Neurology, TUM University Hospital, School of Medicine and Health, Technical University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6322-9545","authenticated-orcid":false,"given":"Albulena","family":"Bajrami","sequence":"additional","affiliation":[{"name":"Neurology Unit, Emergency Department, Ospedale S. Chiara, Azienda per i servizi sanitari (APSS), Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0556-0176","authenticated-orcid":false,"given":"Valeria","family":"Pozzilli","sequence":"additional","affiliation":[{"name":"Neurology and Neurophysiology, Universita Campus Bio-Medico di Roma, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-2297","authenticated-orcid":false,"given":"Matteo","family":"Lucchini","sequence":"additional","affiliation":[{"name":"UOC Neurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Centro di Ricerca per la Sclerosi Multipla \u201cAnna Paola Batocchi,\u201d Dipartimento di Neuroscienze, Facolta di Medicina e Chirurgia, Universita Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0450-7699","authenticated-orcid":false,"given":"Elena","family":"Barbuti","sequence":"additional","affiliation":[{"name":"A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Department of Neurology, University of Rome La Sapienza, Ospedale Sant\u2019Andrea, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3523-4520","authenticated-orcid":false,"given":"Frederik","family":"Bartels","sequence":"additional","affiliation":[{"name":"Department of Neurology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6909-6109","authenticated-orcid":false,"given":"Robert","family":"Barket","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University Innsbruck Clinic of Neurology, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-0442","authenticated-orcid":false,"given":"Christian","family":"Cordano","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences, University of California San Francisco Weill Institute for Neurosciences, San Francisco, CA, USA; Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-6784","authenticated-orcid":false,"given":"Bernhard","family":"Hemmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, TUM University Hospital, School of Medicine and Health, Technical University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Technical University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7703-0553","authenticated-orcid":false,"given":"Alessandro","family":"Cagol","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Switzerland; Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine,University Hospital Basel and University of Basel, Switzerland; Department of Health Sciences (DISSAL), University of Genoa, Biostatistics Unit, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5460-2977","authenticated-orcid":false,"given":"Irene","family":"Schiavetti","sequence":"additional","affiliation":[{"name":"Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Health Sciences (DISSAL), University of Genoa, Biostatistics Unit, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-104X","authenticated-orcid":false,"given":"Maria Pia","family":"Sormani","sequence":"additional","affiliation":[{"name":"Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Health Sciences (DISSAL), University of Genoa, Biostatistics Unit, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ECTRIMS Winter School 2024 study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01473-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02742-w"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01314-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1601277"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0902533"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/17562864211066751"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/1756285617708911"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02435.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12576"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.104970"},{"key":"e_1_3_3_12_2","article-title":"Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial","volume":"9","author":"Cutter G","year":"2023","unstructured":"Cutter G, Rudick RA, de Moor C, et al. Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial. Mult Scler J Exp Transl Clin 2023; 9: 20552173231169463.","journal-title":"Mult Scler J Exp Transl Clin"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-00955-x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004683"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3997"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00009-6"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104662"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007032"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200258"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2010.02.007"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24018"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21606"},{"key":"e_1_3_3_23_2","unstructured":"Study Quality Assessment Tools. National Heart L and Blood Institute July 2021 https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools (accessed 4 March 2025)."},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003653"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209357"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209444"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000205500"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-329221"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2415988"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.09.059"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25145"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-329020"},{"key":"e_1_3_3_33_2","article-title":"Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis","volume":"10","author":"Barro C","year":"2022","unstructured":"Barro C, Healy BC, Liu Y, et al. Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2022; 10: e200052.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458509106937"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.5250"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251407973","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585251407973","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251407973","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:47:34Z","timestamp":1779356854000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585251407973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1177\/13524585251407973"],"URL":"https:\/\/doi.org\/10.1177\/13524585251407973","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}