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Article History

Accepted: 21 January 2025

First Online: 14 February 2025

Declarations

:

: Open Access funding enabled and organized by CAUL and its Member Institutions. The work was supported by grants by the Swiss Science Foundation to J.M. [P500PM_214230 and P5R5PM_225288], and by NHMRC Investigator Grants to T.K. [2026836]. I.R. is supported by a MS Australia postdoctoral fellowship grant. The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva, and Sanofi Genzyme. Design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication were conducted separately and apart from the guidance of the sponsors.

: Jannis Müller received funding from the Swiss National Science Foundation (grant no. P500PM_214230 and P5R5PM_225288). Sifat Sharmin receives research support from MS Australia. Johannes Lorscheider received research support from Innosuisse—Swiss Innovation Agency, the University of Basel, Biogen, and Novartis; received speaker fees, travel support, and/or compensation for advisory boards from Bristol Myers Squibb, Novartis, Roche, and Teva. Dana Horakova was supported by the Charles University: Cooperatio Program in Neuroscience; by the project National Institute for Neurological Research (Program EXCELES, ID project no. LX22NPO5107)—funded by the European Union—Next Generation EU; and by General University Hospital in Prague project MH CZ-DRO-VFN64165. She also received compensation for travel, speaker honoraria, and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva, as well as support for research activities from Biogen Idec. Eva Kubala Havrdova received honoraria/research support from Biogen, Merck Serono, Novars, Roche, and Teva; has been a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novars, and Sanofi Genzyme; received honoraria/research support from Biogen, Merck Serono, Novars, Roche, and Teva; has been a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novars, and Sanofi Genzyme; and has been supported by the Czech Ministry of Education—project Cooperatio LF1, research area Neuroscience, and the project National Institute for Neurological Research (Program EXCELES, ID project no. LX22NPO5107)—funded by the European Union—Next Generation EU. Sara Eichau has received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Janssen, Bristol-Meyers, Bayer, Sanofi Genzyme, Roche, and Teva. Francesco Patti received personal compensation for serving on advisory boards by Almirall, Alexion, Biogen, Bristol, Janssen, Merck, Novartis, and Roche. He further received research grants from Alexion, Almirall, Biogen, Bristol, Merck, Novartis, and Roche, and from FISM, Reload Association (Onlus), Italian Health Minister, and the University of Catania. Pierre Grammond has served in advisory boards for Novartis, EMD Serono, Roche, Biogen idec, Sanofi Genzyme, and Pendopharm, and he has received grant support from Genzyme and Roche. He has received research grants for his institution from Biogen idec, Sanofi Genzyme, and EMD Serono. Katherine Buzzard received speaker honoraria and/or education support from Biogen, Teva, Novartis, Genzyme-Sanofi, Roche, Merck, and Alexion and has been a member of advisory boards for Merck and Biogen. Olga Skibina received honoraria and consulting fees from Bayer Schering, Novartis, Merck, Biogen, and Genzyme. Alexandre Prat has no disclosures to declare. Marc Girard has no disclosures to declare. Francois Grand’Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, and ATARA Pharmaceuticals. Raed Alroughani received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche, and Sanofi-Genzyme. Jeannette Lechner-Scott received travel compensation from Novartis, Biogen, Roche, and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA, and Novartis. Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis, and Sanofi-Aventis, and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva, and Merck. Michael Barnett served on scientific advisory boards for Biogen, Novartis, and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. Elisabetta Cartechini has no disclosures to declare. Maria Jose Sa received consulting fees, speaker honoraria, and/or travel expenses for scientific meetings from Alexion, Bayer Healthcare, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Oliver Gerlach has nothing to disclose. Anneke van der Walt served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck, and Roche She has received speaker’s honoraria and travel support from Novartis, Roche, and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. Helmut Butzkueven has received institutional (Monash University) funding from Biogen, F. Hoffmann-La Roche Ltd, Merck, Alexion, CSL, and Novartis; has carried out contracted research for Novartis, Merck, F. Hoffmann-La Roche Ltd and Biogen; has taken part in speakers’ bureaus for Biogen, Genzyme, UCB, Novartis, F. Hoffmann-La Roche Ltd., and Merck; and has received personal compensation from Oxford Health Policy Forum for the Brain Health Steering Committee. Julie Prevost accepted travel compensation from Novartis, Biogen, Genzyme, and Teva and speaking honoraria from Biogen, Novartis, Genzyme, and Teva. Tamara Castillo-Triviño received speaking/consulting fees and/or travel funding from Almirall, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Bassem Yamout received honoraria as a speaker and member of scientific advisory boards from Sanofi, Bayer, Biogen, Merck, Janssen, Novartis, Roche, and Aspen. Samia J. Khoury received compensation for scientific advisory board activity from Merck and Roche and received compensation for serving on the IDMC for Biogen. Özgür Yaldizli received grants from Swiss National Science Foundation, ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, and the Swiss Multiple Sclerosis Society and received advisory board, lecture, and consultancy fees from Roche, Sanofi Genzyme, Allmirall, Biogen, and Novartis. Tobias Derfuss received speaker fees, research support, travel support, and/or served on advisory boards or steering committees of Alexion, Novartis, Merck, Biogen, GeNeuro, MedDay, Roche, and Sanofi Genzyme. Cristina Granziera’s employer, the University Hospital Basel (USB), has received the following fees which were used exclusively for research support: (i) advisory board and consultancy fees from Actelion, Genzyme-Sanofi, Novartis, GeNeuro, and Roche; (ii) speaker fees from Genzyme-Sanofi, Novartis, GeNeuro, and Roche; and (iii) research support from Siemens, GeNeuro, and Roche. Cristina Granziera is supported by the Swiss National Science Foundation (SNSF) grant PP00P3_176984, the Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung, and the EUROSTAR E!113682 HORIZON2020. Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by the Swiss MS Society, Swiss National Research Foundation (320030_189140/1), University of Basel, Progressive MS Alliance, Alnylam, Bayer, Biogen, Bristol Myers Squibb, Celgene, Immunic, Merck, Neurogenesis, Novartis, Octave Bioscience, Quanterix, Roche, Sanofi, and Stata DX. Ludwig Kappos’ institution (University Hospital Basel) received grants, contracts, or payments from Novartis, Roche, and Innosuisse; consulting fees from AurigaVision, Bayer AG, df-mp Molnia&Pohlman, Genentech, Glaxo Smith Kline, Janssen LLC, Japan Tobacco Inc, Merck, Novartis, Roche, Senda Biosciences Inc, Shionogi BV, and Wellmera AG; payment or honoraria for lectures, presentations, or speaker bureaus from BMS, Celgene, Janssen, Merck, Novartis, and Roche; support for attending meetings and/or travel from MH Consulting, Österreichische Gesellschaft für Neurologie, Novartis Biociencias S.A., and Eli Lilly; payments for advisory boards of Actelion, Merck Healtchcare KGgA, Novartis, Roche, Sanofi, and TG Therapeutics; and payments for participation on data safety monitoring boards of Minoryx Therapeutics S.L. and Santhera Pharmaceuticals. L.K. is an unpaid member of the supervisory board of Neurostatus UHB AG, CEO of the Foundation of Clinical Neuroimmunology and Neuroscience (“RC2N”), MAGNIMS Steering Committee, and board member of the European Charcot Foundation. Izanne Roos has served on scientific advisory boards, received conference travel support and/or speaker honoraria from Roche, Novartis, Merck, and Biogen. Izanne Roos is supported by a MS Australia and the Trish Multiple Sclerosis Research Foundation. Tomas Kalincik served on scientific advisory boards for MS International Federation and World Health Organization, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck, and Biogen; served on the steering committee for the Brain Atrophy Initiative by Sanofi Genzyme; received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL, and Merck; and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck. Tomas Kalincik is an editorial board member of CNS Drugs. Tomas Kalincik was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

: This study received ethics approval from the Melbourne Health Human Research Ethics Committee and the local institutional review boards in all centers.

: Written informed consent was obtained from all patients.

: Not applicable.

: The MSBase registry is a data processor and warehouses data from individual principal investigators who agree to share their datasets on a project-by-project basis. Data access to external parties can be granted on reasonable request at the sole discretion of the principal investigators, who will need to be approached individually for permission.

: The R package MSoutcomes, which was used for the analyses in this study, is openly available on the Comprehensive R Archive Network (CRAN).

: Conception and design of the study: J.M., S.S., J.L., Ö.Y., C.G., T.D., J.K., L.K., I.R., and T.K. Acquisition and analysis of data: J.M., S.S., D.H., E.K.H., S.E., F.P., P.G., K.B., O.S., A.P., M.G., F.G., R.A., J.L.S., D.S., M.B., E.C., M.J.S., O.G., A.V.W., H.B., J.P., T.C.T., B.Y., S.J.K., I.R., and T.K. Drafting a significant portion of the manuscript or figures: J.M., S.S., J.L., D.H., E.K.H., S.E., F.P., P.G., K.B., O.S., A.P., M.G., F.G., R.A., J.L.S., D.S., M.B., E.C., M.J.S., O.G., A.V.W., H.B., J.P., T.C.T., B.Y., S.J.K., Ö.Y., T.D., C.G., J.K., L.K., I.R., and T.K. All authors have read and approved the final submitted manuscript and agree to be accountable for the work.