Summary of Research: Blood Biomarker Dynamics in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study

Heinz Wiendl^{1

2}, Frederik Barkhof^{3

4}, Xavier Montalban⁵, Anat Achiron^{6

7}, Tobias Derfuss⁸, Andrew Chan⁹, Suzanne Hodgkinson¹⁰, Alexandre Prat¹¹, Letizia Leocani^{12

13

14}, Klaus Schmierer^{15

16}, Finn Sellebjerg^{17

18}, Patrick Vermersch¹⁹, Hulin Jin²⁰, Anita Chudecka²¹, Andreas Kloetgen²⁰, Dongdong Lin²², Lidia Gardner²³, Nicola De Stefano²⁴

Affiliations

¹ Department of Neurology, Institute of Translational Neurology, University of Münster, Münster, Germany. heinz.wiendl@uniklinik-freiburg.de.
² Department of Neurology and Neurophysiology, University Medical Center, Freiburg, Breisacher Strasse 64, 79106, Freiburg, Germany. heinz.wiendl@uniklinik-freiburg.de.
³ Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
⁴ Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK.
⁵ Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Valld'Hebron, Barcelona, Spain.
⁶ Multiple Sclerosis Center, Sheba Academic Medical Center, Ramat Gan, Israel.
⁷ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
⁸ Department of Neurology, University Hospital Basel, Basel, Switzerland.
⁹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁰ Ingham Institute for Applied Medical Research, University of New South Wales Medicine and Liverpool Hospital, Sydney, NSW, Australia.
¹¹ Department of Neurosciences, Université de Montréal, Montréal, QC, Canada.
¹² Department of Neurology, University Vita-Salute San Raffaele, Milan, Italy.
¹³ Experimental Neurophysiology Unit, Scientific Institute IRCCS San Raffaele, Milan, Italy.
¹⁴ Department of Neurorehabilitation Science, Casa di Cura Igea, Milan, Italy.
¹⁵ The Blizard Institute, Centre for Neuroscience, Surgery and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
¹⁶ Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS, Trust, London, UK.
¹⁷ Danish MS Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
¹⁸ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁹ Univ. Lille, Inserm U1172 LilNCog, CHU Lille, FHU Precise, Lille, France.
²⁰ Clinical Measurement Sciences, Merck Healthcare KGaA, Darmstadt, Germany.
²¹ Clinical Research Services, Cytel Inc., Geneva, Switzerland.
²² Clinical Measurement Sciences, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA an affiliate of Merck KGaA, Darmstadt, Germany.
²³ Neurology and Immunology Medical Unit, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany.
²⁴ Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.

PMID: 40614039
DOI: 10.1007/s40120-025-00782-2

Free article

Editorial

Summary of Research: Blood Biomarker Dynamics in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study

Heinz Wiendl et al. Neurol Ther. 2025.

Free article

. 2025 Jul 4.

doi: 10.1007/s40120-025-00782-2. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, Institute of Translational Neurology, University of Münster, Münster, Germany. heinz.wiendl@uniklinik-freiburg.de.
² Department of Neurology and Neurophysiology, University Medical Center, Freiburg, Breisacher Strasse 64, 79106, Freiburg, Germany. heinz.wiendl@uniklinik-freiburg.de.
³ Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
⁴ Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK.
⁵ Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Valld'Hebron, Barcelona, Spain.
⁶ Multiple Sclerosis Center, Sheba Academic Medical Center, Ramat Gan, Israel.
⁷ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
⁸ Department of Neurology, University Hospital Basel, Basel, Switzerland.
⁹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁰ Ingham Institute for Applied Medical Research, University of New South Wales Medicine and Liverpool Hospital, Sydney, NSW, Australia.
¹¹ Department of Neurosciences, Université de Montréal, Montréal, QC, Canada.
¹² Department of Neurology, University Vita-Salute San Raffaele, Milan, Italy.
¹³ Experimental Neurophysiology Unit, Scientific Institute IRCCS San Raffaele, Milan, Italy.
¹⁴ Department of Neurorehabilitation Science, Casa di Cura Igea, Milan, Italy.
¹⁵ The Blizard Institute, Centre for Neuroscience, Surgery and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
¹⁶ Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS, Trust, London, UK.
¹⁷ Danish MS Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
¹⁸ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁹ Univ. Lille, Inserm U1172 LilNCog, CHU Lille, FHU Precise, Lille, France.
²⁰ Clinical Measurement Sciences, Merck Healthcare KGaA, Darmstadt, Germany.
²¹ Clinical Research Services, Cytel Inc., Geneva, Switzerland.
²² Clinical Measurement Sciences, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA an affiliate of Merck KGaA, Darmstadt, Germany.
²³ Neurology and Immunology Medical Unit, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany.
²⁴ Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.

PMID: 40614039
DOI: 10.1007/s40120-025-00782-2

Abstract

Cladribine tablets (CladT) for relapsing multiple sclerosis help reset the immune system with short treatment courses over 2 years. This analysis of MAGNIFY-MS contrasted clinical outcomes with changes in immune cells, proteins and genes over 2 years in 270 participants. Most immune cells decreased 3 months after starting CladT. Gradual recovery was seen in naïve, regulatory, and transitional B cells starting at month (M)3 and M6. Gene activity related to immune response changes was also reported. Fewer cells producing pro-inflammatory signals and more cells producing anti-inflammatory signals were detected by M24. Immunoglobulin levels mostly remained normal, and a marker of neuroaxonal damage (serum neurofilament light chain) was decreased. Significant reductions in lesion count occurred from M2 onwards. Annualised relapse rate was 0.11 (95% confidence interval: 0.09, 0.15). Over 90% of participants were free of 6-month confirmed disability progression, around 87% had no confirmed progression on 9-hole peg test and timed 25-foot walk. No significant correlations were seen between clinical parameters and lymphocyte dynamics. The safety profile was consistent with previous studies. These findings provide evidence of CladT rebalancing the immune system towards a more homeostatic and less pathogenic state.

Keywords: Biomarkers; Cladribine tablets; Immune reconstitution therapy; Immunophenotyping; Multiple sclerosis; Transcriptomics.

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Conflict of interest statement

Declarations. Conflict of Interest: Please see original article for full author disclosures. Current affiliation for Heinz Wiendl is Department of Neurology and Neurophysiology, Freiburg University, Freiburg, Germany. Ethical Approval, Consent to Participate, Consent to Publish, Availability of Data and Material: Not applicable.

References

Reference

1. Wiendl H, et al. Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study. Front Immunol. 2025;16:1512189. https://doi.org/10.3389/fimmu.2025.1512189 . - DOI - PubMed - PMC

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Summary of Research: Blood Biomarker Dynamics in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study

Affiliations

Summary of Research: Blood Biomarker Dynamics in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study

Authors

Affiliations

Abstract

Conflict of interest statement

References

Reference

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