Multiple Sclerosis Disease-Modifying Treatment Algorithms: 2025 Positioning of the Portuguese Multiple Sclerosis Study Group

Multiple sclerosis (MS) is a chronic autoimmune-mediated neurodegenerative disease characterized by inflammation, demyelination, and axonal/neuronal damage in the central nervous system. In Portugal, the prevalence of MS is approximately 64.4 per 100 000 individuals. It is typically diagnosed in young adults aged 30 to 40, with a higher incidence in women, although it can also affect children/adolescents and the elderly. Recent advances in MS treatment include the development and approval of several new disease-modifying therapies (DMTs) such as ocrelizumab, cladribine, siponimod, and others, thus expanding options for relapsing-remitting MS (RRMS). However, the options for progressive forms of MS remain limited. In Portugal, MS management strategies, guided by the 2015 recommendations of the Directorate-General of Health and the Portuguese medicines agency, need updating to incorporate recent scientific evidence and clinical expertise. The aim of this manuscript is to highlight gaps in current Portuguese MS treatment algorithms and propose enhancements aligned with global standards, thus improving treatment selection and patient outcomes in the Portuguese healthcare system. Developed by nine Portuguese neurology experts from the Portuguese Multiple Sclerosis Study Group, this document not only provides evidence and clinical practice-based recommendations but also includes DMT algorithms tailored for various MS subtypes, including radiologically and clinically isolated syndromes, RRMS, progressive MS, and specific situations in MS treatment such as pediatric-onset MS, late-onset MS, pregnancy and breastfeeding. This document provides evidence-and clinical practice-based recommendations to optimize decision-making during MS management in Portuguese centers. The experts aim to prompt the urgent revision of national MS treatment frameworks, incorporating the latest advancements in MS research and international guidelines, to reduce the socio-economic burden on the national healthcare system and improve the long-term health outcomes of MS patients.