Observational Study

. 2025 Jul 2;272(8):491.

doi: 10.1007/s00415-025-13221-x.

Comparative effectiveness of teriflunomide and ocrelizumab on smoldering activity in multiple sclerosis: an observational study in the Swiss Multiple Sclerosis Cohort

Alessandro Cagol^{1

2

3

4}, Sabine Schaedelin^{1

5}, Mario Ocampo-Pineda^{1

2

3}, Pascal Benkert⁵, Lester Melie-Garcia^{1

2

3}, Ludovico Luchetti^{6

7}, Özgür Yaldizli^{1

2

3}, Johanna Oechtering^{2

3}, Marcus D'Souza^{2

3}, Bettina Fischer-Barnicol², Stefanie Müller⁸, Sebastian Finkener⁹, Jochen Vehoff⁸, Giulio Disanto¹⁰, Andrew Chan¹¹, Caroline Pot¹², Chiara Zecca^{10

13}, Tobias Derfuss^{2

3}, Johanna M Lieb¹⁴, Michael Diepers¹⁵, Franca Wagner¹⁶, Renaud Du Pasquier^{12

17}, Patrice H Lalive¹⁸, Emanuele Pravatà^{10

13

19}, Olaf Chan-Hi Kim²⁰, Robert Hoepner¹¹, Patrick Roth²¹, Claudio Gobbi^{10

13}, David Leppert², Marco Battaglini^{6

7}, Ludwig Kappos^{1

2

3}, Maria Pia Sormani^{4

22}, Jens Kuhle^{2

3}, Cristina Granziera^{23

24

25}; Swiss MS Cohort

Affiliations

¹ Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Hegenheimermattweg 167b, 4123, Allschwil, Basel, Switzerland.
² Multiple Sclerosis Centre, Departments of Neurology, Clinical Research and Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
³ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
⁴ Dipartimento di Scienze della Salute, Università degli Studi di Genova, Genoa, Italy.
⁵ Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
⁶ Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
⁷ SIENA Imaging SRL, Siena, Italy.
⁸ Clinic of Neurology, HOCH Health Ostschweiz, Cantonal Hospital St. Gallen, Academic and Research Hospital, St. Gallen, Switzerland.
⁹ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁰ Neurology Department, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.
¹¹ Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
¹² Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
¹³ Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
¹⁴ Division of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁵ Department of Diagnostic and Interventional Neuroradiology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁶ Department of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
¹⁷ Division of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
¹⁸ Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹⁹ Department of Neuroscience, Imaging and Clinical Sciences, Institute of Advanced Biomedical Technologies, University of Chieti, 66100, Chieti, Italy.
²⁰ Department of Radiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
²¹ Department of Neurology, University of Zurich, University Hospital of Zurich, Zurich, Switzerland.
²² IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
²³ Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Hegenheimermattweg 167b, 4123, Allschwil, Basel, Switzerland. cristina.granziera@usb.ch.
²⁴ Multiple Sclerosis Centre, Departments of Neurology, Clinical Research and Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland. cristina.granziera@usb.ch.
²⁵ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland. cristina.granziera@usb.ch.

PMID: 40603656
PMCID: PMC12222313
DOI: 10.1007/s00415-025-13221-x

Observational Study

Comparative effectiveness of teriflunomide and ocrelizumab on smoldering activity in multiple sclerosis: an observational study in the Swiss Multiple Sclerosis Cohort

Alessandro Cagol et al. J Neurol. 2025.

. 2025 Jul 2;272(8):491.

doi: 10.1007/s00415-025-13221-x.

Authors

Affiliations

¹ Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Hegenheimermattweg 167b, 4123, Allschwil, Basel, Switzerland.
² Multiple Sclerosis Centre, Departments of Neurology, Clinical Research and Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
³ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
⁴ Dipartimento di Scienze della Salute, Università degli Studi di Genova, Genoa, Italy.
⁵ Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
⁶ Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
⁷ SIENA Imaging SRL, Siena, Italy.
⁸ Clinic of Neurology, HOCH Health Ostschweiz, Cantonal Hospital St. Gallen, Academic and Research Hospital, St. Gallen, Switzerland.
⁹ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁰ Neurology Department, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.
¹¹ Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
¹² Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
¹³ Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
¹⁴ Division of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁵ Department of Diagnostic and Interventional Neuroradiology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁶ Department of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
¹⁷ Division of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
¹⁸ Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹⁹ Department of Neuroscience, Imaging and Clinical Sciences, Institute of Advanced Biomedical Technologies, University of Chieti, 66100, Chieti, Italy.
²⁰ Department of Radiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
²¹ Department of Neurology, University of Zurich, University Hospital of Zurich, Zurich, Switzerland.
²² IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
²³ Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Hegenheimermattweg 167b, 4123, Allschwil, Basel, Switzerland. cristina.granziera@usb.ch.
²⁴ Multiple Sclerosis Centre, Departments of Neurology, Clinical Research and Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland. cristina.granziera@usb.ch.
²⁵ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland. cristina.granziera@usb.ch.

PMID: 40603656
PMCID: PMC12222313
DOI: 10.1007/s00415-025-13221-x

Abstract

Background: This study aimed to compare the effects of teriflunomide and ocrelizumab on clinical and MRI endpoints related to smoldering activity in relapsing-remitting multiple sclerosis (RRMS).

Methods: In this observational, longitudinal, multicenter study, we included 128 people with RRMS (pwRRMS) treated with teriflunomide and 495 treated with ocrelizumab. Outcomes included time to progression independent of relapse activity (PIRA). In a subset, we also assessed brain volume loss (BVL), longitudinal changes in diffusion tensor imaging (DTI) metrics, and the burden of paramagnetic rim lesions (PRLs). Propensity score matching was used for between-group comparisons.

Results: Over a median follow-up of 3.1 years in the ocrelizumab group and 1.9 years in the teriflunomide group, there were no significant differences in the risk of PIRA (HR for teriflunomide vs. ocrelizumab: 0.80 [95%-CI:0.40-1.60]; p = 0.53). PwRRMS treated with teriflunomide exhibited lower annualized rates of BVL (-0.80 [95%-CI: -0.91; -0.69] vs. -1.06 [95%-CI: -1.25; -0.86]; p = 0.025) and gray matter volume loss (-0.92 [95%-CI: -1.05; -0.79] vs. -1.20 [95%-CI: -1.43; -0.97]; p = 0.035). No differences were observed in DTI metrics or PRL count.

Conclusions: This real-world study suggests that teriflunomide shows similar efficacy to ocrelizumab on smoldering activity, with a potentially greater effect in reducing BVL. Further research is needed to confirm these findings and understand their long-term implications.

Keywords: Disease-modifying therapies; Ocrelizumab; PIRA; PRLs; Smoldering MS; Teriflunomide.

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Conflict of interest statement

Declarations. Conflict of interest: A. Cagol has received speaker honoraria from Novartis and Roche. S. Schadelin, M. Ocampo-Pineda, P. Benkert, L. Melie-Garcia, L. Luchetti, C. Pot, S. Finkener, G. Disanto, J. M. Lieb, F. Wagner, O. Chan-Hi Kim have nothing to disclose. Ö. Yaldizli received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board/lecture and consultancy fees from Roche, Sanofi Genzyme, Allmirall, Biogen and Novartis. J. Oechtering received research support by the Swiss MS Society and served on advisory boards for Roche and Merck. M. D’Souza, Michael Diepers, R. Du Pasquier, M. Battaglini have nothing to disclose in relation to this work. B. Fisher-Barnicol reported personal fees from Biogen outside the submitted work. S. Müller received honoraria for travel, honoraria for lectures/consulting, and/or grants for studies from Almirall, Biogen, Celgene, Novartis, Teva, Merck Serono, Genzyme, Roche, and Bayer Schweiz. J. Vehoff received honoraria for travel, honoraria for lectures/consulting and/or grants for studies from Allmiral, Biogen, Novartis, Teva, Merck-Serono, Genzyme, Roche and Bayer Schweiz AG, none related to this work. A. Chan has served on advisory boards for, and received funding for travel or speaker honoraria from, Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche, and Teva, all for hospital research funds; and research support from Biogen, Genzyme and UCB. A. Chan is associate editor of the European Journal of Neurology and serves on the editorial board for Clinical and Translational Neuroscience and as topic editor for the Journal of International Medical Research. C. Zecca’ institution the Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland receives financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis. T. Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Alexion, Biogen, Celgene, GeNeuro, MedDay, Merck, Novartis, Roche and Sanofi-Genzyme; he received research support from Alexion, Biogen, Novartis, Roche, Swiss National Research Foundation, University of Basel, and Swiss MS Society. P. H. Lalive received honoraria for speaking and or travel expense from Biogen, Merck, Novartis, Roche; consulting fees from Biogen, GeNeuro, Merck, Novartis, Roche; research support from Biogen, Merck, Novartis. None were related to this work. E. Pravatà received honoraria for serving on scientific advisory boards from Bayer AG, unrelated to the present work. R. Hoepner received speaker/advisor honorary from Merck, Novartis, Roche, Biogen, Alexion, Sanofi, Janssen, Bristol-Myers Squibb, Teva/Mepha and Almirall. He received research support within the last 5 years from Roche, Merck, Sanofi, Biogen, Chiesi, and Bristol-Myers Squibb. He also received research grants from the Swiss MS Society, the SITEM Insel Support Fund and is a member of the Advisory Board of the Swiss and International MS Society. He also serves as deputy editor in chief for Journal of Central Nervous System disease and is part of the ECTRIMS Young Investigator Committee. P. Roth has received honoraria for lectures or advisory board participation from Alexion, Bristol-Myers Squibb, Boehringer Ingelheim, CDR-Life, Debiopharm, Galapagos, Laminar, Midatech Pharma, Novocure, OM Pharma, QED, Roche, Sanofi and Servier and research support from Merck Sharp and Dohme and TME Pharma. C. Gobbi’s institution, the Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland received financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis. PHL received honoraria for speaking from Biogen-Idec, CSL Bering, Merck Serono, Novartis, Sanofi-Aventis, Teva; consulting fees from Biogen-Idec, Geneuro, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; research grants from Biogen-Idec, Merck Serono, Novartis. D. Leppert is Chief Medical Officer of GeNeuro. L. Kappos has received no personal compensation. His institutions (University Hospital Basel/Foundation Clinical Neuroimmunology and Neuroscience Basel) have received and used exclusively for research support: payments for steering committee and advisory board participation, consultancy services, and participation in educational activities from: Actelion, Bayer, BMS, df-mp Molnia & Pohlmann, Celgene, Eli Lilly, EMD Serono, Genentech, Glaxo Smith Kline, Janssen, Japan Tobacco, Merck, MH Consulting, Minoryx, Novartis, F. Hoffmann-La Roche Ltd, Senda Biosciences Inc., Sanofi, Santhera, Shionogi BV, TG Therapeutics, and Wellmera, and license fees for Neurostatus-UHB products; grants from Novartis, Innosuisse, and Roche. M. P. Sormani received consulting fees from Biogen, Merck, Novartis, Roche, Sanofi, Immunic, Alexion. J. 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, Bayer, Biogen, Bristol Myers Squibb, Celgene, Immunic, Merck, Neurogenesis, Novartis, Octave Bioscience, Quanterix, Roche, Sanofi, Stata DX. C. Granziera: The University Hospital Basel (USB) and the Research Center for Clinical neuroimmunology and Neuroscience (RC2NB), as the employers of Cristina Granziera, have received the following fees which were used exclusively for research support from Siemens, GeNeuro, Genzyme-Sanofi, Biogen, Roche. They also have received advisory board and consultancy fees from Actelion, Genzyme-Sanofi, Novartis, GeNeuro, Merck, Biogen and Roche; as well as speaker fees from Genzyme-Sanofi, Novartis, GeNeuro, Merck, biogen and Roche.

Figures

**Fig. 1**
Study design. Abbreviations: 3D-EPI = three-dimensional echo planar imaging; 3D-MPRAGE = three-dimensional magnetization-prepared rapid gradient echo; DTI = diffusion tensor imaging; DWI = diffusion-weighted imaging; PIRA = progression independent of relapse activity; PRL = paramagnetic rim lesion; PS = propensity score

**Fig. 2**
Probability of PIRA-free survival. Abbreviations: PIRA = progression independent of relapse activity

**Fig. 3**
Between group comparison of brain volume loss rates

See this image and copyright information in PMC

References

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Comparative effectiveness of teriflunomide and ocrelizumab on smoldering activity in multiple sclerosis: an observational study in the Swiss Multiple Sclerosis Cohort

Affiliations

Comparative effectiveness of teriflunomide and ocrelizumab on smoldering activity in multiple sclerosis: an observational study in the Swiss Multiple Sclerosis Cohort

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources