Multiple sclerosis: emerging epidemiological trends and redefining the clinical course.

Multiple sclerosis is a chronic, inflammatory, and neurodegenerative disease of the central nervous system and a major cause of neurological disability in young adults. Its prevalence and incidence are increasing, and it has been estimated at over 2.8 million cases worldwide, in addition to recent trends towards a shift in MS prevalence to older ages, with peak prevalence estimates in the sixth decade of life. Although historically the relapsing and progressive phases of the disease have been considered separate clinical entities, recent evidence of progression independent of relapse activity (PIRA) has led to a reconsideration of multiple sclerosis as a continuum, in which relapsing and progressive features variably coexist from the earliest stages of the disease, challenging the traditional view of the disease course. In this Series article, we provide an overview of how the traditional description of the clinical course of MS and epidemiological trends in Europe have evolved. For this purpose, we focus on the concept of PIRA, discussing its potential as the main mechanism by which patients acquire disability, how its definition varies between studies, and ongoing research in this field. We emphasise the importance of incorporating the assessment of hidden clinical manifestations into patient management to help uncover and quantify the PIRA phenomenon and the possible implications for future changes in the clinical classification of the disease. At the same time, we provide insights into overcoming the challenges of identifying and defining PIRA and adopting a new understanding of the clinical course of MS.

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© 2024 The Author(s).

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E. Portaccio received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, participation on a Data Safety Monitoring Board or Advisory Board and support for attending meetings and/or travel from Biogen, Merck Serono, Sanofi, Teva, Roche, BMS Cellgene, Janssen and Novartis. M. Magyari received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Merck, Novartis, Roche, Sanofi, Bristol Myers Squibb and for participation on a Data Safety Monitoring Board or Advisory Board from Sanofi, Novartis, Merck, Moderna. E.K. Havrdova received grants or contracts from Czech Ministry of Education—project Cooperatio LF1, research area Neuroscience and the project National Institute for Neurological Research (Programme EXCELES, ID project No LX22NPO5107), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Actelion (Janssen/J&J), Biogen, Celgene (BMS), Merck, Novartis, Roche, Sanofi and Teva and for participation on a Data Safety Monitoring Board or Advisory Board from Actelion (Janssen/J&J), Biogen, Celgene (BMS), Merck, Novartis, Roche and Sanofi. A. Ruet received grants or contracts from BMS Celgene, Roche, Biogen, Sanofi Genzyme, Merck, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Merck, Sanofi Genzyme and support for attending meetings and/or travel from Alexion, Biogen, Novartis. B Brochet received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and support for attending meetings and/or travel from BMS Celgene, Merck Serono, Roche and for participation on a Data Safety Monitoring Board or Advisory Board from BMS Celgene, Merck Serono, Novartis, Roche and Sanofi. A. Scalfari reports no disclosures relevant to this manuscript. M. Di Filippo received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, participation on a Data Safety Monitoring Board or Advisory Board and support for attending meetings and/or travel from Alexion, BMS, Bayer, Biogen Idec, Genzyme, Horizon, Janssen, Merck, Mylan, Novartis, Roche, Siemens Healthineers, Teva and Viatris. Carmen Tur received grants or contract from Junior Leader La Caixa Fellowship (fellowship code is LCF/BQ/PI20/11760008), awarded by “la Caixa” Foundation (ID 100010434), Miguel Servet Contract (CP23/00117), awarded by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation and FORTALECE grant (FORT23/00034), awarded by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Novartis, Bristol Myers Squibb, Johnson and Johnson, Immunic AG, and Merck; support for attending meetings and/or travel, participation on a Data Safety Monitoring Board or Advisory Board from Roche, Novartis, Bristol Myers Squibb, and Merck. X. Montalban received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, participation on a Data Safety Monitoring Board or Advisory Board and support for attending meetings and/or travel from AbbVie, Actelion, Alexion, Biogen, BMS/Celgene, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, MedDay, Merck, Mylan, NervGen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, EXCEMED, MSIF and NMSS. M.P. Amato received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, participation on a Data Safety Monitoring Board or Advisory Board and support for attending meetings and/or travel from Biogen Idec, Merck Serono, Bayer Schering Pharma, and Sanofi Aventis.