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Article History

Received: 2 March 2026

Revised: 30 April 2026

Accepted: 9 May 2026

First Online: 21 May 2026

Declarations

:

: F Romanò has nothing to disclose. P Valsasina has nothing to disclose. M Albergoni has nothing to disclose. M.P. Amato received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, and Teva Pharmaceutical Industries, and receives research support from Biogen Idec, Merck-Serono, Roche, Pharmaceutical Industries and Fondazione Italiana Sclerosi Multipla (FISM). G Brichetto has been awarded and receives research support from Roche, FISM, ARSEP, H2020 EU Call. In the last 3 years, J Chataway has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust, he is supported in part by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre, London, UK, he has been a local principal investigator for a trial in MS funded by the Canadian MS society, a local principal investigator for commercial trials funded by: Ionis, Novartis and Roche, and has taken part in advisory boards/consultancy for Azadyne, Biogen, Lucid, Janssen, Merck, NervGen, Novartis and Roche. N. D. Chiaravalloti is on an Advisory Board for Akili Interactive and is a member of the Editorial Boards of Multiple Sclerosis Journal and Frontiers in NeuroTrauma. G Cutter is a member of Data and Safety Monitoring Boards for Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Horizon Pharmaceuticals, Hisun Pharmaceuticals, Mapi Pharmaceuticals LTD, Merck, Merck/Pfizer, Opko Biologics, OncoImmune, Neurim, Novartis, Ophazyme, Sanofi Aventis, Reata Pharmaceuticals, Teva pharmaceuticals, VielaBio Inc, Vivus, NHLBI (Protocol Review Committee), NICHD (OPRU oversight committee), he is on Consulting or Advisory Boards for Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Klein-Buendel Incorporated, Medimmune, Medday, Neurogenesis LTD, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Roche, TG Therapeutics, he is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc, a private consulting company located in Birmingham AL. U Dalgas has received research support, travel grants, and/or teaching honorary from Biogen Idec, Merck-Serono, Novartis, Bayer Schering, and Sanofi Aventis as well as honoraria from serving on scientific advisory boards of Biogen Idec and Genzyme. J DeLuca is an Associate Editor of the Archives of Physical Medicine and Rehabilitation, and Neuropsychology Review, received compensation for consulting services and/or speaking activities from Biogen Idec, Celgene, MedRhythms, and Novartis, and receives research support from Biogen Idec, National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers, and National Institutes of Health. R Farrel has received honoraria and served on advisory panels for Merck, TEVA, Novartis, Genzyme, GW pharma (Jazz pharmaceuticals), Allergan, Merz, Ipsen and Biogen, she is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. P Feys is editorial board member of NNR, MSJ and Frontiers in Rehabilitation Sciences (section ‘Strengthening Health Systems’), provides consultancy to NeuroCompass and was board of advisory board meetings for Biogen. J Freeman has been awarded research grants from the NIHR, UK. M Inglese is Co-Editor for Controversies for Multiple Sclerosis Journal, received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, and received research support from NIH, NMSS, the MS Society of Canada, the Italian Ministry of Health, FISM, H2020 EU Call. E Cipriano has nothing to disclose. C Meza has nothing to disclose. R.W. Motl has nothing to disclose. A Salter receives research funding from Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, CMSC and the US Department of Defense, and is a member of editorial board for Neurology, and serves as a consultant for Gryphon Bio, LLC, Sora Neuroscience and Abata Therapeutics. She has equity in Owl Therapeutics. B. M. Sandroff has nothing to disclose. A Feinstein is on Advisory Boards for Akili Interactive and Roche, and reports grants from the MS Society of Canada, book royalties from Johns Hopkins University Press, Cambridge University Press, Amadeus Press and Glitterati Editions, and speaker’s honoraria from Novartis, Biogen, Roche and Sanofi Genzyme. M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Roche; and speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Celgene, Horizon Therapeutics Italy, Merck Serono SpA, Mitsubishi-Tanabe Pharma, Neuraxpharm, Novartis, Roche, Sandoz, and Sanofi. She receives research support from the MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and FISM. She is Associate Editor for Multiple Sclerosis and Related Disorders ; and Associate Co-Editor for Europe and Africa for Multiple Sclerosis Journal . M Filippi is Editor-in-Chief of the Journal of Neurology , Associate Editor of Human Brain Mapping , Neurological Sciences, and Radiology ; received compensation for consulting services from Almirall, Biogen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Roche, Sanofi; speaking activities from Amgen, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Chiesi Italia SpA, Eisai, Eli Lilly, Fujirebio, Genzyme, Janssen, Merck, Neopharmed Gentili, Neuraxpharm, Novartis, Novo Nordisk, Roche, Sanofi, Takeda; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Eli Lilly, GE Healthcare Ltd, Merck, Neuraxpharm, Novartis, Roche, Sandoz, Sanofi, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and FISM.

: This study involving human participants was approved by Ethical standards committees on human experimentation of the participating sites (the Kessler Foundation Institutional Review Board (Protocol #R-1017–18); University of Alabama Birmingham IRB (IRB300002637); Comitato Etico Regionale N. Registro CER Liguria 294bis/2018; IRCCS Ospedale San Raffaele Ethical committee (124/INT/2018)). Participants gave informed consent to participate in the study before taking part in accordance to the Helsinki Declaration (Fortaleza revision, 2013).

: The authors did not use generative AI and AI-assisted technologies during the preparation of this work.

: The main trial was registered on ClinicalTrials.gov (NCT03679468; registration date: 20 Sep 2018).