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Review
. 2025 Feb 1;272(2):179.
doi: 10.1007/s00415-025-12917-4.

Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion

Massimo Filippi  1   2   3   4   5 , Maria Pia Amato  6   7 , Carlo Avolio  8   9 , Paolo Gallo  10   11 , Claudio Gasperini  12 , Matilde Inglese  13   14 , Girolama Alessandra Marfia  15 , Francesco Patti  16   17
Affiliations
Review

Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion

Massimo Filippi et al. J Neurol. .

Abstract

The classification of multiple sclerosis (MS) into the two distinct phases of relapsing-remitting and progressive, including primary progressive and secondary progressive phenotypes (PPMS and SPMS, respectively) has long been accepted; however, there are several unmet needs associated with this particular model. The observation that both inflammation and neurodegeneration are present from the onset of MS has resulted in a paradigm shift towards MS as a disease continuum driven by pathological mechanisms underlying clinical progression. Here we report the results from a meeting of Italian MS specialists, exploring the evolving perception of MS pathobiology and its implications for diagnosis and treatment. Insights garnered from the expert panel advocate for a redefined understanding of MS. This expert opinion paper reviews the disease continuum and the intertwined nature of inflammatory and neurodegenerative processes. Also, the need for changes in diagnostic criteria and treatment strategies, including the development of novel biomarkers and new therapies targeting smouldering disease, is discussed.

Keywords: Bruton’s tyrosine kinase inhibitor; Italy; Multiple sclerosis; Progression independent of relapse activity; Relapse; Smouldering multiple sclerosis.

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Conflict of interest statement

Declarations. Competing interests: MF 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 Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA, participation in Advisory Boards for Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, 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 Fondazione Italiana Sclerosi Multipla; MPA has served on Scientific Advisory Boards for Biogen, Merck, Novartis, Roche, Sanofi, and Teva Pharmaceuticals; has received speaker honoraria from Biogen, Merck, Novartis, Roche, Sanofi, and Teva Pharmaceuticals; CA has received honoraria for speaking, consultation fees and research grants from Biogen, Merck, Novartis, Roche, Sanofi, Bristol Myers Squibb, Alexion, and Amgen; and he is an Advisory Board member of Alexion, Amgen, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, and Sanofi. PG has received grants and personal fees from Biogen Idec, Sanofi-Genzyme, and Merck Serono; grants and personal fees from Novartis; grants from the Department of Neuroscience, University of Padua; grants from the Veneto Region of Italy; grants from the Italian Association for Multiple Sclerosis (AISM); and grants from the Italian Ministry of Public Health. CG has received fees as an invited speaker or travel expenses for attending meetings from Biogen, Genzyme, Merck Serono, Mylan, Novartis, Sanofi, Almirall, Astra Zeneca, Sandoz; MI has received grants from the Italian Multiple Sclerosis Society Foundation (FISM), the Italian National Institute of Health, and the National MS Society (NMSS); has received fees for consultation from Biogen, Bristol Myers Squibb, Genzyme, Janssen, Merck, Novartis, Roche, and Sanofi. GAM is an Advisory Board member of Biogen Idec, Sanofi-Genzyme, Merck-Serono, Novartis, F. Hoffmann-La Roche and received grant/contract support, honoraria and consultation fees from Almirall, Amgen, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, F. Hoffmann-La Roche, Mylan, Alexion, Janssen Cilag and Bristol Myers Squibb. She is the principal investigator in clinical trials for Biogen Idec, Merck Serono, Novartis, F. Hoffmann-La Roche, Sanofi-Genzyme, Merck Serono and Bristol Myers Squibb. FP has received honoraria for speaking activities from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva Pharmaceuticals; he has served as an Advisory Board member for Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva Pharmaceuticals; received funds from Pfizer, and the Italian Multiple Sclerosis Society Foundation (FISM), for epidemiological studies.

Figures

Fig. 1
Fig. 1
The multiple sclerosis paradigm has shifted from distinct clinical phenotypes to a continuum of clinical manifestations in which the key target is the prevention of disability accumulation. CNS central nervous system, MS multiple sclerosis
See this image and copyright information in PMC

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