Advances and challenges in the treatment of Multiple Sclerosis: The role of disease-modifying therapies
DOI:
https://doi.org/10.36557/2674-8169.2026v8n5p380-399Keywords:
Multiple sclerosis, Disease-modifying therapies, Monoclonal antibodies, TreatmentAbstract
Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system, characterized by demyelination and progressive neurological disability. Although it has no cure, therapeutic advances have significantly expanded disease control possibilities, especially through disease-modifying therapies (DMTs), which act on different immunological mechanisms. This study aimed to analyze the advances and challenges related to the use of DMTs in the treatment of multiple sclerosis, highlighting their mechanisms of action, clinical efficacy, limitations, and future perspectives based on recent evidence. This is an integrative literature review guided by the research question regarding the disease-modifying therapies in the context of MS and their main advances and challenges. The search was conducted in the PubMed, SciELO, MEDLINE, and LILACS databases using descriptors combined with the Boolean operator “AND.” Articles published in the last five years, with full-text availability and compatible methodology, were included. The results indicate that high-efficacy therapies, such as anti-CD20 monoclonal antibodies and natalizumab, significantly reduce inflammatory activity and disease progression. However, limitations related to safety, therapeutic individualization, and low penetration into the central nervous system remain. Emerging approaches, such as BTK inhibitors and the use of biomarkers and artificial intelligence, show promise for future treatment strategies. In conclusion, despite significant advances in MS management, therapeutic decisions should be individualized, considering clinical characteristics and treatment response, and should integrate inflammatory control, neuroprotection, and personalized medicine.
Downloads
References
AL ANBER, Arwa et al. Therapeutic outcomes of fingolimod and interferon beta-1a in relapsing–remitting multiple sclerosis: a real-world study from Jordan. Medicina, v. 62, p. 203, 2026.
ARISI, Ivan et al. Cladribine and ocrelizumab induce differential miRNA profiles in peripheral blood mononucleated cells from relapsing–remitting multiple sclerosis patients. Frontiers in Immunology, v. 14, 2023.
BAR-OR, Amit et al. Clinical perspectives on the molecular and pharmacological attributes of anti-CD20 therapies for multiple sclerosis. CNS Drugs, v. 35, p. 985–997, 2021.
BOU RJEILY, Nicole et al. Highly effective therapy versus escalation approaches in early multiple sclerosis. Neurologic Clinics, v. 42, n. 1, p. 185–201, 2024.
BRASIL, Ministério da Saúde.Aprova o Protocolo Clínico e Diretrizes Terapêuticas da Esclerose Múltipla (EM). Portaria Conjunta SAES/SECTICS nº 8, de 12 de setembro de 2024. Brasília: Ministério da Saúde, 2024
CALFUNAO, Susan et al. Siponimod (BAF312): características generales e implicancias clínicas de la dosificación farmacogenómica en el tratamiento de la esclerosis múltiple secundaria progresiva. Revista Médica de Chile, v. 151, p. 1375–1384, 2023.
CENCIONI, Maria et al. B cells in multiple sclerosis — from targeted depletion to immune reconstitution therapies. Nature Reviews Neurology, v. 17, p. 399–414, 2021.
CHMIELEWSKA, Natalia et al. Targeting CD20 in multiple sclerosis — review of current treatment strategies. Neurologia i Neurochirurgia Polska, v. 57, n. 3, p. 235–242, 2023.
CHISARI, Clara Grazia et al. Effectiveness of rituximab in relapsing multiple sclerosis previously treated with highly active disease modifying therapies (RENEGADE study). Journal of Neurology, v. 273, n. 47, 2026.
CONTENTTI, Edgar Carnero et al. Current perspectives: evidence to date on BTK inhibitors in the management of multiple sclerosis. Drug Design, Development and Therapy, v. 16, p. 2249–2263, 2022.
COYLE, Patricia et al. Sphingosine 1-phosphate receptor modulators in multiple sclerosis treatment: a practical review. Annals of Clinical and Translational Neurology, v. 11, n. 4, p. 842–855, 2024.
DE SÈZE, Jérôme et al. Anti-CD20 therapies in multiple sclerosis: from pathology to the clinic. Frontiers in Immunology, v. 14, 2023.
DUMITRESCU, L. et al. Beta interferons as immunotherapy in multiple sclerosis: a new outlook on a classic drug during the COVID-19 pandemic. QJM: An International Journal of Medicine, v. 114, p. 691-697, 2021.
FRANCESCHINI, Alessandro et al. Lesion location and functional connections reveal cognitive impairment networks in multiple sclerosis. Annals of Clinical and Translational Neurology, v. 13, p. 242-255, 2025.
FRISCH, Esther et al. A milestone in multiple sclerosis therapy: monoclonal antibodies against CD20—Yet progress continues. Neurotherapeutics,v. 18, p. 1602-1622, 2021.
GELADARIS, Anastasia et al. Bruton’s tyrosine kinase inhibitors in multiple sclerosis: pioneering the path towards treatment of progression? CNS Drugs, v. 36, p. 1019-1030 2022.
HARTUNG, Hans-Peter et al. Bioavailable central nervous system disease-modifying therapies for multiple sclerosis. Frontiers in Immunology, v. 14, e1290666, 2023.
JEANTIN, Lina et al. Natalizumab extended-interval dosing in a real-life setting. Journal of the Neurological Sciences, v. 450, e120689, 2023.
KAPPOS, Ludwig et al. Ocrelizumab exposure in relapsing–remitting multiple sclerosis: 10-year analysis of the phase 2 randomized clinical trial and its extension. Journal of Neurology, v. 271, p. 642–657, 2024.
LAMBERT, Clare McGarvey et al. Real-world infection risk in multiple sclerosis patients on long-term immunomodulatory treatments. Multiple Sclerosis and Related Disorders, v. 94, e106236, 2024.
LEREIM, Ragnhild Reehorst et al. Natalizumab promotes anti-inflammatory and repair effects in multiple sclerosis. PLoS ONE, v.19, e0300914.
LORENZUT, Simone et al. Exploring the Pathophysiology, Diagnosis, and Treatment Options of Multiple Sclerosis. Journal of integrative neuroscience, v. 24, n. 1, p. 25081, Spring 2025.
MAERSK-MOLLER, Camilla et al. A national Danish effectiveness study of ocrelizumab versus natalizumab in multiple sclerosis. European Journal of Neurology, n. 2, e70507, 2025.
MARGONI, Monica et al. Anti‐CD20 therapies for multiple sclerosis: current status and future perspectives. Journal of Neurology, v. 269, n. 3, p. 1203–1217, 2022.
MARTIN, Sarah-Jane; ARSENAULT, Shane; OH, Jiwon. A drug evaluation narrative review of cladribine as a treatment for multiple sclerosis. Neurodegenerative Disease Management, v. 15, n. 6, p. 323–339, 2025.
MOCCIA, M. et al. Utilization of peginterferon-β-1a in the real-world practice for relapsing-remitting multiple sclerosis. European Review for Medical and Pharmacological Sciences, v. 28, p. 411–418, 2024.
MOHAMMED, Eiman et al. Understanding multiple sclerosis pathophysiology and current disease-modifying therapies: a review of unaddressed aspects. Frontiers in Bioscience (Landmark Edition), v. 29, n. 11, 2024.
MONSCHEIN, Tobias et al. Real‐world use of natalizumab in Austria: data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR). Journal of Neurology, v. 270, p.3779-3786, 2023.
MORADI, Nahidi et al. Neurofilament Light Chain Concentration in the Prediction of Treatment Response in Multiple Sclerosis. European Journal of Neurology, v. 33, e70505, 2026.
MORALES, Yanet Valdés; MESA, Carlos Jorge Hidalgo; CABRERA, Yalina Beatriz Bravo. Importancia de la predicción temprana de la atrofia cerebral en pacientes con esclerosis múltiple. Medicent Electrón, v. 28, e4270, 2024.
PIACENTINI, Chiara et al. Cognitive impairment in multiple sclerosis: “classic” knowledge and recent acquisitions. Arquivos de Neuro-Psiquiatria, v. 81, p. 585–596, 2023.
PIEHL, F. Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis. Journal of internal medicine. v. 289, p. 771-791.
QUEIROZ, André Luiz Guimarães de et al. Plasma exchange in inflammatory demyelinating disorders of the central nervous system: reasonable use in the clinical practice. Arquivos de Neuro-Psiquiatria, v. 81, p. 296–307, 2023.
ROWLES, William et al. Transitioning from S1P receptor modulators to B cell–depleting therapies in multiple sclerosis: clinical, radiographic, and laboratory data. Neurology: Neuroimmunology & Neuroinflammation, v. 9, e1183, 2022.
SABERI, Darius et al. Bruton’s tyrosine kinase as a promising therapeutic target for multiple sclerosis. Expert Opinion on Therapeutic Targets, v. 27, n. 4-5, p. 347–359, 2023.
SAPONARO, Anne-Charlotte et al. Treatments of paediatric multiple sclerosis: efficacy and tolerance in a longitudinal follow-up study. European Journal of Paediatric Neurology, v. 45, p. 22–28, 2023.
SPELMAN, Tim et al. Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom. Journal of Medical Economics, v. 27, n. 1, p. 109–125, 2024.
WEATHERLEY, Georgia et al. Therapeutic targeting of oligodendrocytes in an agent-based model of multiple sclerosis. PLoS Computational Biology, v. 22, n. 1, e1013273, 2026.
WESSELS, Hendrik et al. Pharmacokinetic and pharmacodynamic similarity of biosimilar natalizumab (PB006) to its reference medicine: a randomized controlled trial. Expert Opinion on Biological Therapy, v. 23, n. 12, p. 1287–1297, 2023.
WILLARD, Charles et al. Combined magnetic resonance imaging and serum analysis reveals distinct multiple sclerosis types. Brain, v. 148, p. 4578–4591, 2025.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Rebeca Tazo Miosso , Eduarda Fernanda da Silva Costa, Natã Pereira Mariano , Raquel Kato Loureiro , Julia Onodera Shinohara , Rafaela Tinasso Castelo Branco , Yasmin Fernandes Abdelnur, Dioelen Virginia Borges Souza de Aquino Coelho
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors are copyright holders under a CCBY 4.0 license.
