Ahmed Abdelhak, Franziska Bachhuber, Kiarra Ning, Pascal Benkert, W John Boscardin, Aleksandra Maleska Maceski, Sabine Schaedelin, Lutz Achtnichts, Sebastian Finkener, Patrice H Lalive, Marjolaine Uginet, Caroline Pot, Renaud Du Pasquier, Robert Hoepner, Andrew Chan, Claudio Gobbi, Chiara Zecca, Stefanie Müller, Patrick Roth, Cristina Granziera, Tanuja Chitnis, Evan Madill, Howard L Weiner, Ari J Green, Stephen L Hauser, Bruce Ac Cree, Tania Kümpfel, Joachim Havla, Thomas Skripuletz, Stefan Gingele, Makbule Senel, Ioannis Vardakas, Daniela Taranu, Ulf Ziemann, Markus C Kowarik, Ingo Kleiter, Muna-Miriam Hoshi, Uwe K Zettl, Axel Haarmann, Simon Thebault, Mark S Freedman, Hailey P Bergman, Ellen Iacobaeus, Mohsen Khademi, Diana Ferraro, Martina Cardi, Sara Mariotto, Manuel Comabella, Xavier Montalban, Andreu Vilaseca-Jolonch, Eva M Strijbis, Mark Hj Wessels, Joep Killestein, Bernhard Hemmer, Friederike Held, Finn Sellebjerg, Helene Højsgaard Chow, Roberto Alvarez-Lafuente, Maria Inmaculada Domínguez-Mozo, Harald Hegen, Klaus Berek, Florian Deisenhammer, Eric Thouvenot, Hanane Agherbi, Konrad Rejdak, Magda Gąsior, Dimitrios Tzanetakos, John S Tzartos, Maria Pia Sormani, Irena Dujmovic Basuroski, Georgina Arrambide, Michael Khalil, Fredrik Piehl, Charlotte E Teunissen, Jens Kuhle, Hayrettin Tumani
{"title":"预测进行性多发性硬化症残疾恶化的血液生物标志物：一项跨国、个体参与者水平的分析。","authors":"Ahmed Abdelhak, Franziska Bachhuber, Kiarra Ning, Pascal Benkert, W John Boscardin, Aleksandra Maleska Maceski, Sabine Schaedelin, Lutz Achtnichts, Sebastian Finkener, Patrice H Lalive, Marjolaine Uginet, Caroline Pot, Renaud Du Pasquier, Robert Hoepner, Andrew Chan, Claudio Gobbi, Chiara Zecca, Stefanie Müller, Patrick Roth, Cristina Granziera, Tanuja Chitnis, Evan Madill, Howard L Weiner, Ari J Green, Stephen L Hauser, Bruce Ac Cree, Tania Kümpfel, Joachim Havla, Thomas Skripuletz, Stefan Gingele, Makbule Senel, Ioannis Vardakas, Daniela Taranu, Ulf Ziemann, Markus C Kowarik, Ingo Kleiter, Muna-Miriam Hoshi, Uwe K Zettl, Axel Haarmann, Simon Thebault, Mark S Freedman, Hailey P Bergman, Ellen Iacobaeus, Mohsen Khademi, Diana Ferraro, Martina Cardi, Sara Mariotto, Manuel Comabella, Xavier Montalban, Andreu Vilaseca-Jolonch, Eva M Strijbis, Mark Hj Wessels, Joep Killestein, Bernhard Hemmer, Friederike Held, Finn Sellebjerg, Helene Højsgaard Chow, Roberto Alvarez-Lafuente, Maria Inmaculada Domínguez-Mozo, Harald Hegen, Klaus Berek, Florian Deisenhammer, Eric Thouvenot, Hanane Agherbi, Konrad Rejdak, Magda Gąsior, Dimitrios Tzanetakos, John S Tzartos, Maria Pia Sormani, Irena Dujmovic Basuroski, Georgina Arrambide, Michael Khalil, Fredrik Piehl, Charlotte E Teunissen, Jens Kuhle, Hayrettin Tumani","doi":"10.1136/jnnp-2025-335831","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Biologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS).</p><p><strong>Methods: </strong>Data were collected from BioMS-eu network centres and collaborating cohorts. pwPMS with primary progressive MS (PPMS) or secondary progressive MS (SPMS) with at least one GFAP value and at least three follow-up expanded disability status scale (EDSS) scores were included. The prognostic value of serum GFAP and NfL age- and sex-adjusted Z-scores for future CDW was evaluated using Cox regression models, accounting for sex, age, baseline disease duration and EDSS, and dominant treatment during follow-up.</p><p><strong>Results: </strong>1058 participants and 7530 encounters were included (median age 53 years (IQR: 44 to 59), 57% female, follow-up 4.6 years (2.9 to 8.4)) with median baseline GFAP of 0.74 (-0.10 to 1.55) and NfL of 0.64 (-0.36 to 1.51). 723 CDW events were recorded. Each GFAP Z-score increase was associated with ~10% higher CDW risk (adjusted HR (aHR) 1.107 (1.001 to 1.225), p=0.049). Results were mainly driven by SPMS participants (n=613, aHR 1.242 (1.073 to 1.438), p=0.004). Higher NfL Z-scores predicted CDW only in PPMS participants (1.236 (1.092 to 1.399), p=0.001).</p><p><strong>Conclusions: </strong>GFAP was a prognostic indicator for future CDW in pwPMS, especially in pwSPMS. On the other hand, NfL was predictive of CDW only in pwPPMS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis.\",\"authors\":\"Ahmed Abdelhak, Franziska Bachhuber, Kiarra Ning, Pascal Benkert, W John Boscardin, Aleksandra Maleska Maceski, Sabine Schaedelin, Lutz Achtnichts, Sebastian Finkener, Patrice H Lalive, Marjolaine Uginet, Caroline Pot, Renaud Du Pasquier, Robert Hoepner, Andrew Chan, Claudio Gobbi, Chiara Zecca, Stefanie Müller, Patrick Roth, Cristina Granziera, Tanuja Chitnis, Evan Madill, Howard L Weiner, Ari J Green, Stephen L Hauser, Bruce Ac Cree, Tania Kümpfel, Joachim Havla, Thomas Skripuletz, Stefan Gingele, Makbule Senel, Ioannis Vardakas, Daniela Taranu, Ulf Ziemann, Markus C Kowarik, Ingo Kleiter, Muna-Miriam Hoshi, Uwe K Zettl, Axel Haarmann, Simon Thebault, Mark S Freedman, Hailey P Bergman, Ellen Iacobaeus, Mohsen Khademi, Diana Ferraro, Martina Cardi, Sara Mariotto, Manuel Comabella, Xavier Montalban, Andreu Vilaseca-Jolonch, Eva M Strijbis, Mark Hj Wessels, Joep Killestein, Bernhard Hemmer, Friederike Held, Finn Sellebjerg, Helene Højsgaard Chow, Roberto Alvarez-Lafuente, Maria Inmaculada Domínguez-Mozo, Harald Hegen, Klaus Berek, Florian Deisenhammer, Eric Thouvenot, Hanane Agherbi, Konrad Rejdak, Magda Gąsior, Dimitrios Tzanetakos, John S Tzartos, Maria Pia Sormani, Irena Dujmovic Basuroski, Georgina Arrambide, Michael Khalil, Fredrik Piehl, Charlotte E Teunissen, Jens Kuhle, Hayrettin Tumani\",\"doi\":\"10.1136/jnnp-2025-335831\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Biologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS).</p><p><strong>Methods: </strong>Data were collected from BioMS-eu network centres and collaborating cohorts. pwPMS with primary progressive MS (PPMS) or secondary progressive MS (SPMS) with at least one GFAP value and at least three follow-up expanded disability status scale (EDSS) scores were included. The prognostic value of serum GFAP and NfL age- and sex-adjusted Z-scores for future CDW was evaluated using Cox regression models, accounting for sex, age, baseline disease duration and EDSS, and dominant treatment during follow-up.</p><p><strong>Results: </strong>1058 participants and 7530 encounters were included (median age 53 years (IQR: 44 to 59), 57% female, follow-up 4.6 years (2.9 to 8.4)) with median baseline GFAP of 0.74 (-0.10 to 1.55) and NfL of 0.64 (-0.36 to 1.51). 723 CDW events were recorded. Each GFAP Z-score increase was associated with ~10% higher CDW risk (adjusted HR (aHR) 1.107 (1.001 to 1.225), p=0.049). Results were mainly driven by SPMS participants (n=613, aHR 1.242 (1.073 to 1.438), p=0.004). Higher NfL Z-scores predicted CDW only in PPMS participants (1.236 (1.092 to 1.399), p=0.001).</p><p><strong>Conclusions: </strong>GFAP was a prognostic indicator for future CDW in pwPMS, especially in pwSPMS. On the other hand, NfL was predictive of CDW only in pwPPMS.</p>\",\"PeriodicalId\":16418,\"journal\":{\"name\":\"Journal of Neurology, Neurosurgery, and Psychiatry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.7000,\"publicationDate\":\"2025-06-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology, Neurosurgery, and Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jnnp-2025-335831\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology, Neurosurgery, and Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jnnp-2025-335831","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis.
Background and objectives: Biologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS).
Methods: Data were collected from BioMS-eu network centres and collaborating cohorts. pwPMS with primary progressive MS (PPMS) or secondary progressive MS (SPMS) with at least one GFAP value and at least three follow-up expanded disability status scale (EDSS) scores were included. The prognostic value of serum GFAP and NfL age- and sex-adjusted Z-scores for future CDW was evaluated using Cox regression models, accounting for sex, age, baseline disease duration and EDSS, and dominant treatment during follow-up.
Results: 1058 participants and 7530 encounters were included (median age 53 years (IQR: 44 to 59), 57% female, follow-up 4.6 years (2.9 to 8.4)) with median baseline GFAP of 0.74 (-0.10 to 1.55) and NfL of 0.64 (-0.36 to 1.51). 723 CDW events were recorded. Each GFAP Z-score increase was associated with ~10% higher CDW risk (adjusted HR (aHR) 1.107 (1.001 to 1.225), p=0.049). Results were mainly driven by SPMS participants (n=613, aHR 1.242 (1.073 to 1.438), p=0.004). Higher NfL Z-scores predicted CDW only in PPMS participants (1.236 (1.092 to 1.399), p=0.001).
Conclusions: GFAP was a prognostic indicator for future CDW in pwPMS, especially in pwSPMS. On the other hand, NfL was predictive of CDW only in pwPPMS.
期刊介绍：
The Journal of Neurology, Neurosurgery & Psychiatry (JNNP) aspires to publish groundbreaking and cutting-edge research worldwide. Covering the entire spectrum of neurological sciences, the journal focuses on common disorders like stroke, multiple sclerosis, Parkinson’s disease, epilepsy, peripheral neuropathy, subarachnoid haemorrhage, and neuropsychiatry, while also addressing complex challenges such as ALS. With early online publication, regular podcasts, and an extensive archive collection boasting the longest half-life in clinical neuroscience journals, JNNP aims to be a trailblazer in the field.
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