{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:29:20Z","timestamp":1786350560517,"version":"build-2736575974"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Roche Pharma AG"},{"name":"Universit\u00e4tsklinikum D\u00fcsseldorf. Anstalt \u00f6ffentlichen Rechts"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising multiple sclerosis (MS) biomarkers, but biological confounding and inter-assay variability limit real-world use. We assessed whether Z score normalisation enables platform-agnostic monitoring in people with MS (pwMS) under ocrelizumab, and which early timepoint best stratifies subsequent biomarker trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This pooled multicentre analysis of three German cohorts included pwMS treated with ocrelizumab for\u2009\u2265\u200912\u00a0months. Elecsys\n                      <jats:sup>\u00ae<\/jats:sup>\n                      or Simoa\n                      <jats:sup>\u00ae<\/jats:sup>\n                      assays were harmonised using covariate-adjusted Z scores. We evaluated biomarker 24-month trajectories and whether stratification and relative reductions predicted 24-month biomarker-status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>430 pwMS were included [78% relapsing MS (RMS), 22% primary progressive MS (PPMS)]. Baseline sNfL Z scores were higher in RMS; sGFAP Z scores were similar. Multivariable analyses linked higher expanded disability status scale to elevation of both biomarkers, while younger age was independently associated with higher sNfL. Following ocrelizumab, sNfL decreased in RMS while sGFAP remained stable. People with RMS and concurrent baseline elevation sustained the highest levels, diverging from the stable PPMS profile. Month-12 combined elevation best predicted persisting 24-month elevation, outperforming baseline and 6-month assessments. Crucially, failing to achieve a\u2009\u2265\u200950% relative reduction at month 12 strongly predicted persistent 24-month elevation for sNfL (OR 7.14, 95% CI 1.35\u201337.75) and sGFAP (OR 32.08, 95% CI 5.10\u2013201.67).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Z score normalisation enabled platform-agnostic framework for MS monitoring of downstream biological trajectories. We identify a practical 12-month exploratory responder threshold: pwMS failing to reach a\u2009\u2265\u200950% relative Z score reduction represent a group with persistent biomarker elevation, supporting closer clinical surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13986-9","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:59:40Z","timestamp":1783677580000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From measurement to biomarker trajectories: platform-agnostic Z score analysis of serum NfL and GFAP in ocrelizumab-treated multiple sclerosis"],"prefix":"10.1007","volume":"273","author":[{"given":"Hernan","family":"Inojosa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Masanneck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Akg\u00fcn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Hagler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Schulze-Bosse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Benkert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Ruprecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pawlitzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjalf","family":"Ziemssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"13986_CR1","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","volume":"372","author":"A Compston","year":"2008","unstructured":"Compston A, Coles A (2008) Multiple sclerosis. 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Lars Masanneck reports no conflicts of interest related to this study. He has received honoraria for lecturing, consulting, and travel expenses for attending meetings from Biogen, Merck, Sanofi, argenX, Neuraxpharm, Bial, Roche, Alexion, and Novartis, all outside the scope of this work. His research is funded by the German Multiple Sclerosis Foundation (DMSG), the B.Braun Foundation and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)\u2014493659010. Katja Akg\u00fcn received personal compensation from Novartis, Biogen Idec, Teva, Sanofi, and Roche for consulting services. LW and RH have nothing to declare. Ramona Hagler reports no disclosures. Sven G. Meuth reports Honoraria\/travel support from Academy2, Argenx, AstraZeneca, Bayer, Biontech, Celgene, Datamed, Desitin, Diaplan, DIU, Dpmed, Gen Medicine & Healthcare, IGES, Impulze GmbH, KW Medipoint, MedDay, Medmile, MICE, Mylan, Neuraxpharm, Neurapharm, Oxford PharmaGenesis, QuintilesIMS, Sanofi, Springer, STADA, Chugai, UCB, Viatris, Wings for Life int, and Xcenda. Research support from BMBF, BfR, DFG, EKFS, G-BA, Hertie Fdn, IZKF, DGN, Ministry of Culture & Science NRW, Daimler & Benz Fdn, dmsg, Peek & Cloppenburg Fdn, Hempel Fdn, German Alzheimer Society, Bayer, BMS, Demecan, Diamed, Genzyme, Hexal, Janssen, MerckSerono, Novartis, NovoNordisk, ONO Pharma, Roche, and Teva. Carolin Otto is the Principal Investigator of the CRC NeuroMac funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) \u2013 Project-ID 259373024 \u2013 TRR 167. Patrick Schindler received speaker\u2019s honoraria, travel support and\/or served on advisory boards by Alexion, Roche, and UCB. Karin Schulze-Bosse no disclosures. Jens Kuhle received speaker fees, research support, travel support, and\/or served on advisory boards by Swiss MS Society, Swiss National Research Foundation (320030_212534\/1), University of Basel, Progressive MS Alliance, Alnylam, Argenx, Bayer, Biogen, Bristol Myers Squibb, Celgene, Immunic, Merck, Neurogenesis, Novartis, Octave Bioscience, Quanterix, Roche, Sanofi, Stata DX. Pascal Benkert: no disclosures. Klemens Ruprecht has received research support from the European Union (821283-2), Stiftung Charit\u00e9, Guthy-Jackson Charitable Foundation, and Arthur Arnstein Foundation; and received speaker\u2019s honoraria from Virion Serion and Novartis. Marc Pawlitzki received honoraria for lecturing and travel expenses for attending meetings from Alexion, ArgenX, Bayer Health Care, Biogen, Hexal, Merck Serono, Novartis, Roche, Sanofi-Aventis, Takeda and Teva. His research is funded by ArgenX, Biogen, Demecan, Hexal, Horizon Merck Serono, Novartis, Roche, Viatris, Takeda and Teva, all outside the scope of this work. His research is funded by the German Multiple Sclerosis Foundation (DMSG), the B. Braun Foundation and the German Alzheimer Society. Tjalf Ziemssen reports personal fees from Biogen, BMS, Merck, Neuraxpharm, Novartis, Novo Nordisk, Roche, Sanofi, Sandoz, Teva, and Viatris; and research support from Genzyme, Neuraxpharm, Novartis, Roche, Sanofi, and Teva.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Participants were drawn from three independent cohorts: the D\u00fcsseldorf cohort, the Dresden cohort, and the CONTACT study cohort. All cohorts received ethical approval from the respective ethics committees (University Hospital Duesseldorf (2021-1475, 5951R, and 2024-2817) and Review Board of the University Hospital of Dresden (EK331112009, EK3480920149) in accordance with the ethical principles set forth in the Helsinki Declaration of 1975, as revised in 1983, and the guidelines on good pharmacovigilance practices.","order":2,"name":"Ethics","label":"Ethics statement","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"454"}}