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Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS., (© The Author(s), 2024.)

Introduction: The Spasticity-Plus Syndrome (SPS) in multiple sclerosis (MS) refers to a combination of spasticity and other signs/symptoms such as spasms, cramps, bladder dysfunction, tremor, sleep disorder, pain, and fatigue. The main purpose is to develop a user-friendly tool that could help neurologists to detect SPS in MS patients as soon as possible., Methods: A survey research based on a conjoint analysis approach was used. An orthogonal factorial design was employed to form 12 patient profiles combining, at random, the eight principal SPS signs/symptoms. Expert neurologists evaluated in a survey and a logistic regression model determined the weight of each SPS sign/symptom, classifying profiles as SPS or not., Results: 72 neurologists participated in the survey answering the conjoint exercise. Logistic regression results of the survey showed the relative contribution of each sign/symptom to the classification as SPS. Spasticity was the most influential sign, followed by spasms, tremor, cramps, and bladder dysfunction. The goodness of fit of the model was appropriate (AUC = 0.816). Concordance between the experts' evaluation vs. model estimation showed strong Pearson's ( r  = 0.936) and Spearman's ( r  = 0.893) correlation coefficients. The application of the algorithm provides with a probability of showing SPS and the following ranges are proposed to interpret the results: high (> 60%), moderate (30-60%), or low (< 30%) probability of SPS., Discussion: This study offers an algorithmic tool to help healthcare professionals to identify SPS in MS patients. The use of this tool could simplify the management of SPS, reducing side effects related with polypharmacotherapy., Competing Interests: ÓF has received honoraria in the past as consultant in advisory boards, and as chairmen or lecturer in meetings, and has also participated or participates at present in clinical trials and other research projects promoted by Biogen, Bayer, Merck-Serono, Teva, Novartis, Actelion, Almirall, Roche, Allergan, Horizon, and Ala Diagnostics. LC-F has served at scientific advisory boards, participated in meetings sponsored by and received speaking honoraria or travel funding or research grants from Biogen, Bristol-Myers Squibb, Janssen, Horizon, Merck-Serono, Novartis, Roche and Sanofi. MM has received honoraria as speaker, consultant in advisory boards, travel support or research grants from Merck, Biogen, Novartis, Sanofi-Genzyme, Almirall, Viatris, Horizon, Bristol-Myers Squibb, Roche, Sandoz and Janssen. PM has received compensation for consulting services and speaking fees from Allergan, Almirall, Biogen, Merz and Sanofi. JP has served as consultant, speaker and/or moderator for Bayer Pharmaceuticals, Biogen, Bristol-Myers Squibb, Daiichi Sankyo, Genzyme Corporation, Janssen, Merck Serono, Novartis, Sanofi, Sandoz, Teva, Roche Pharma, Almirall and Celgene. LR-T has received compensation for consulting services and speaking fees from Biogen, Novartis, Bayer, Merck, Sanofi, Genzyme, Roche, Bristol-Myers Squibb, Teva and Janssen. AM has received honoraria for scientific and commercial activities from Biogen, Teva, Merck, Sanofi, Novartis, Roche, Almirall, and Mylan. YA has received research grants, travel support and lecturing and consulting fees from Bayer, Biogen, Roche, Merck, Novartis, Almirall, Sanofi-Genzyme, Janssen and Bristol-Myers Squibb. AA has received honoraria as a speaker or advisor from Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche and Sanofi. EÁ has received collaborations and fees for participation in advisories, scientific and educational activities from Almirall, Biogen, Janssen Cilag, Sanofi-Genzyme, Merck, Novartis, Roche and Teva. AL-F reports no disclosures relevant to the manuscript. LL has received collaborations and fees for participation in advisories, scientific and educational activities, from Almirall, Bayer, Biogen, Bristol-Myers Squibb, Sanofi-Genzyme, Merck, Novartis, UCB Pharma, Roche and Teva. EM has received honoraria as consultant in advisory boards, and or as chairperson or lecturer in meetings, attendance to congresses and has also participated in clinical trials and other research projects promoted by Almirall, Bayer, Biogen, Bristol Myers Squibb, Janssen, Merck, Teva, Novartis, Roche, Sandoz and Sanofi-Genzyme. PO-N has received collaborations and fees for participation in advisories, scientific and educational activities from Almirall, Biogen, Bristol-Myers Squibb, Sanofi-Genzyme, Merck, Novartis, UCB Pharma, Roche and Teva., (Copyright © 2024 Fernández Fernández, Costa-Frossard, Martínez Ginés, Montero Escribano, Prieto González, Ramió-Torrentà, Aladro, Alonso Torres, Álvarez Rodríguez, Labiano-Fontcuberta, Landete Pascual, Miralles Martínez, Moral Torres and Oliva-Nacarino.)

Background: Updated information about self-reported experience and satisfaction with care of MS patients (PwMS) in Spain is scarce. We aim to describe, from PwMS' perspective, the disease impact, the quality of life and the satisfaction level with the social and healthcare support in Spain, and its evolution over the last decade., Methods: Multicentre observational study, based on a cross-sectional nationwide survey, completed by 432 PwMS in Spain throughout 2018. The results were compared with those of a similar study carried out in 2007 (370 patients), whose database was retrieved as baseline information., Results: 432 patients recruited from 61 neurology units fully completed the study e-survey (mean age: 43.7 years; 71.4% women). The personal profile of patients was largely similar between the 2007 and 2018 samples. The proportion of patients who identified themselves as having relapsing-remitting MS was higher in 2018 (77.1% vs. 56.7 in 2007; p = 0.0001). Overall, 2018 patients considered themselves more labour-active, less disabled, more independent in movement, and as higher family income earners. The proportion of patients satisfied or very satisfied with healthcare services accessibility increased over time (54.9% in 2007 vs. 66.2 in 2018; p = 0.0009). Similarly, more patients considered their health condition to be good or very good in 2018 (55.8% vs. 33.7% in 2007; p = 0.0001). In contrast, there seems to be little progress in social support terms and opportunities equality., Conclusions: Health condition of PwMS seems to have improved over the last decade, which could be the result of an increasingly effective health care. However, more social protection measures are needed., (Copyright © 2021. Published by Elsevier B.V.)

Background: Updated information on the self-perceived biopsychosocial burden and the healthcare experience among people living with multiple sclerosis in Spain is scarce.We aim to describe the self-reported disease experience of patients diagnosed with MS in Spain and to estimate their biopsychosocial burden., Methods: Multicentre epidemiological study based on a cross-sectional nationwide survey completed by a geographically stratified sample of MS patients in Spain., Results: A total of 490 surveys completed at 61 neurology units across Spain were analysed. Mean age was 43.7 ± 10.0 years (range:21-72), 71.4% were women. Most patients identified themselves as having relapsing-remitting MS (77.1%), 81.9% retained independent mobility. Most patients considered their health condition to be good (39.4%) or very good (13.1%). Mean EuroQoL questionnaire score was 69.2 ± 21.5. Most patients expressed high level of satisfaction with access to and quality of health care. However, 53.7% considered that sadness or depression interfered with their daily life. Concerns about social support were also mentioned., Conclusion: Most people living with MS in Spain consider that their health condition is at least good but more psychological support and social protection measures are needed. Insights obtained from this study may help to better manage the condition in the future., (Copyright © 2021. Published by Elsevier B.V.)

Background: Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease that in many cases produces disability, having a high impact in patients' lives, reducing significantly their quality of life. The aim of this study was to agree on a set of proposals to improve the current management of MS within the Spanish National Health System (SNHS) and apply the Social Return on Investment (SROI) method to measure the potential social impact these proposals would create., Methods: A Multidisciplinary Working Team of nine experts, with representation from the main stakeholders regarding MS, was set up to agree on a set of proposals to improve the management of MS. A forecast SROI analysis was carried out, with a one-year timeframe. Data sources included an expert consultation, a narrative literature review and a survey to 532 MS patients. We estimated the required investment of a hypothetical implementation, as well as the potential social value that it could create. We calculated outcomes in monetary units and we measured intangible outcomes through financial proxies., Results: The proposed ideal approach revealed that there are still unmet needs related to MS that can be addressed within the SNHS. Investment would amount to 148 million € and social return to 272 million €, so each euro invested could yield almost €2 of social return., Conclusions: This study could guide health interventions, resulting in money savings for the SNHS and increases in patients' quality of life.

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis., Objective: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain., Development: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group., Conclusion: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice., (Copyright © 2019 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Peripheral blood biomarkers able to predict disease activity in multiple sclerosis (MS) patients have not been identified yet. Here, we analyzed the immune phenotype of T lymphocyte subpopulations in peripheral blood samples from 66 RRMS patients under DMF ( n = 22) or fingolimod ( n = 44) treatment, by flow cytometry. A correlation study between the percentage and absolute cell number of each lymphocyte subpopulation with the presence of relapses or new MRI lesions during 12-month follow-up was performed. Patients who had undergone relapses showed at baseline higher percentage of Th1 CM cells (relapsed: 11.60 ± 4.17% vs . nonrelapsed: 9.25 ± 3.17%, p < 0.05) and Th1Th17 CM cells (relapsed: 15.65 ± 6.15% vs . nonrelapsed: 10.14 ± 4.05%, p < 0.01) before initiating DMF or fingolimod treatment. Kaplan-Meier analysis revealed that patients with Th1Th17 CM (CD4 + CCR7 + CD45RA - CCR6 + CXCR3 + ) cells > 11.48% had a 50% relapse-free survival compared to patients with Th1Th17 CM cells < 11.48% whose relapse-free survival was 88% ( p = 0.013, log-rank test). Additionally, a high percentage of Th1Th17 CM cells was also found in patients with MRI activity (MRI activity: 14.02 ± 5.87% vs . no MRI activity: 9.82 ± 4.06%, p < 0.01). Our results suggest that the percentage of Th1Th17 CM lymphocytes at baseline is a predictive biomarker of activity during the first 12 months of treatment, regardless of the treatment.

Aims: Fingolimod, an orally active immunomodulatory drug for relapsing-remitting multiple sclerosis (RRMS), sequesters T cells in lymph nodes through functional antagonism of the sphingosine-1-phosphate receptor, reducing the number of potential autoreactive cells that migrate to the central nervous system. However, not all RRMS patients respond to this therapy. Our aim was to test the hypothesis that by immune-monitoring RRMS patient's leukocyte subpopulations it is possible to find biomarkers associated with clinical response to fingolimod., Methods: Prospective study. Analysis of peripheral blood mononuclear cell subpopulations by multiparametric flow cytometry, at baseline and +1, +3, +6, +12 months of follow-up in 40 RRMS patients starting fingolimod therapy., Results: Fingolimod treatment induced a severe lymphopenia affecting mainly T and B cells. A relative increase in T reg (memory T reg : 3.8 ± 1.0% baseline vs 8.8 ± 4.4% month +1; activated T reg : 1.5 ± 0.7% baseline vs 3.7 ± 2.1% month +1, P < 0.001) as well as transitional B cells (10.5 ± 12.3% baseline vs 18.7 ± 14.6% month +1, P < 0.001) was observed. Interestingly, lymphocyte subpopulations were already at baseline significantly different in responder patients. The percentage of recent thymic emigrants (RTE) used to stratify fingolimod responder, and no responder patients was the best biomarker (4.0 ± 1.4% vs 7.4 ± 1.9%, respectively [P < 0.001])., Conclusion: The results support that immune-monitoring of lymphocyte subpopulations in peripheral blood is a promising tool to select RRMS candidate for fingolimod treatment., (© 2018 John Wiley & Sons Ltd.)