Treatment Of Multiple Sclerosis Research Articles

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD). Furthermore, treatment and monitoring protocols, rehabilitation and other supportive care before and after AHSCT need to be optimized. To address these issues, we convened a European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop in partnership with the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party, in which evidence and key questions were presented and discussed by experts in these diseases and in AHSCT. Based on the workshop output and subsequent written interactions, this Consensus Statement provides practical guidance and recommendations on the use of AHSCT in MS and NMOSD. Recommendations are based on the available evidence, or on consensus when evidence was insufficient. We summarize the key evidence, report the final recommendations, and identify areas for further research.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS. A list of therapies with anti-EBV effects was developed from existing reviews. A detailed review of pre-clinical and clinical data was undertaken to assess these candidates for potential usefulness and possible harm in MS. A 'drug-CV' and a plain language version focusing on tolerability aspects was created for each candidate. We used validated criteria to score each candidate with an international scientific panel and people living with MS. A preliminary list of 11 drug candidates was generated. Following review by the scientific and lived experience expert panels, six yielded the same highest score. A further review by the expert panel shortlisted four drugs (famciclovir, tenofovir alafenamide, maribavir and spironolactone) deemed to have the best balance of efficacy, safety and tolerability for use in MS. Scientific and lived experience expert panel review of anti-EBV therapies selected four candidates with evidence for efficacy against EBV and acceptable safety and tolerability for potential use in phase III clinical trials for MS.

Whole blood concentrations of fingolimod and its pharmacologically active metabolite fingolimod phosphate obtained during routine health care of patients with multiple sclerosis.

Fingolimod is a first-in-class, orally administered drug indicated for the treatment of relapsing-remitting multiple sclerosis. It acts as an immunomodulator, is classified as a "disease-modifying therapy", and its main mechanism of action is the modulation of sphingosine-1-phosphate receptors. In this prospective pilot study, whole blood concentrations of fingolimod and fingolimod phosphate obtained during routine health care were measured. In this study, we aimed to determine whether therapeutic monitoring of fingolimod and fingolimod phosphate concentrations can help personalise pharmacotherapy for patients with multiple sclerosis. The study group consisted of 73 patients treated with oral fingolimod (0.5 mg) once daily. Blood samples were collected between July 2021 and January 2022. The whole blood concentrations of fingolimod and fingolimod phosphate were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The relationship between the measured concentrations and the absolute peripheral blood lymphocyte count was evaluated. Fingolimod concentrations ranged from 0.61 to 6.21 µg/L, and fingolimod phosphate concentrations from 0.48 to 4.28 µg/L. Significantly higher concentrations of the active metabolite, fingolimod phosphate, and a significantly higher fingolimod phosphate/fingolimod concentration ratio were observed in women. The sum of fingolimod and fingolimod phosphate concentrations was significantly higher in the subgroup of patients with a lower absolute peripheral blood lymphocyte count. Although all patients were treated with the same dose of fingolimod (0.5 mg orally daily), a 10-fold difference was observed in the achieved whole blood concentrations of fingolimod and fingolimod phosphate. This wide inter-individual variability may lead to potential toxicity or suboptimal concentrations, with the risk of further deterioration in the clinical condition of patients with multiple sclerosis. Therefore, fingolimod is a suitable candidate for therapeutic drug monitoring, including monitoring patient adherence to treatment.

Identifying Cladribine prescription pattern in MS: an Italian multicentre study.

Characterizing Cladribine tablets prescription pattern in daily clinical practice is crucial for optimizing multiple sclerosis (MS) treatment. To describe efficacy, safety profile and new disease-modifying therapy (DMT) prescriptions following Cladribine treatment. Independent retrospective cohort study in patients followed at six Italian MS centres. Patients diagnosed with relapsing MS (RMS) according to 2017 McDonald criteria, who initiated Cladribine between January 2019 and May 2023, were included. A generalized linear regression model was built for the outcome DMT after Cladribine course. Heatmaps were generated based on weighted pivot tables to visualize the proportion of patients requiring DMT post-Cladribine. A total cohort of 352 patients was enrolled, 134 naïve to any DMT, 218 switchers from other DMTs. The last DMT was an injectable first-line DMT for 48 (22%) patients, oral first-line DMT for 141 (64.7%) patients, SP1 inhibitor-Fingolimod for 23 (10.6%) patients, and Natalizumab for 6 (2.7%) patients. Overall, Cladribine was efficacious and well tolerated, 12% of patients required a new DMT prescription after a median time of 24 months. The regression model revealed that patients aged >40 years at Cladribine prescription had a 16% decrease in likelihood of receiving a new DMT. Heatmaps showed patients previously on Fingolimod had a lower rate (72.2%) of being free from therapy after Cladribine. In our multicentric real-world Italian study, Cladribine therapy is generally effective during the investigated follow-up period. Understanding key characteristics of patients responding best to Cladribine can help tailor therapeutic strategies for optimal outcomes.

Effect of alemtuzumab on fatigue, quality of life, and patient/caregiver-reported outcomes in relapsing-remitting multiple sclerosis – a real-world evidence study

BackgroundAlemtuzumab is approved in the European Union for treating highly active relapsing-remitting multiple sclerosis (RRMS). Patient-reported outcomes measure the treatment impact on quality of life (QoL), including fatigue, a common symptom in multiple sclerosis (MS). Chronic diseases like MS also affect the patient's caregiver. Thus, understanding the impact on both patients and caregivers is essential for a comprehensive view of MS treatment outcomes. MethodsThis multi-center prospective, observational study assessed RRMS patients undergoing alemtuzumab treatment, and their caregivers across three European countries (Denmark, Norway, and Italy). The study visits were conducted at baseline, and at Months 3, 6, 12, 18, 24, and 36 (± 1 month). The primary endpoint assessed the effect of alemtuzumab on MS-related fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC] score). Secondary endpoints included changes in cognition (Symbol Digit Modalities Test [SDMT]), depression (Beck Depression Inventory-Version II [BDI-II]), QoL (29-item Multiple Sclerosis Impact Scale [MSIS-29]), treatment satisfaction (Treatment Satisfaction Questionnaire for Medication [TSQM]), working capacity/daily life activity (Health-Related Productivity Questionnaire [HRPQ]), and clinical evaluation (number of relapses, improvement in Expanded Disability Status Scale [EDSS] score, and need for re-treatment with alemtuzumab/any other treatment). Exploratory endpoints included caregiver perception of patient's QoL, caregiver QoL, and caregiver burden. The sample size (N=80) was determined based on the 2-sided t-test at 5% significance level. Data were analyzed descriptively. Safety was also evaluated. ResultsOf 87 enrolled patients, 72.4% (n=63) completed all follow-ups. Significant improvement was observed in fatigue (p<0.01), with a median (min, max) FSMC score change of -7.3 (-56.0, 34.0) units at the end-of-study (EOS), and clinically relevant improvement (≥ 9 units) noted in approximately 12.5 months. SDMT (3-5 units, p<0.05), BDI-II (median score of 9.5, i.e., no depression, p<0.01), and MSIS-29 (median change in physical and psychological impact scores -9.2, p<0.01 and -14.8, p<0.001, respectively) improved significantly from baseline to EOS. Global treatment satisfaction (p<0.001), effectiveness (p<0.05), and side effects (p<0.05) significant improved exept at EOS, whereas treatment convenience remained same throughout the study. The percentage of patients with at least one relapse was similar each year of the study (10.8%-13.2%). A statistically significant improvement (p<0.05) in EDSS was reported over time. At EOS, 4.5% patients needed retreatment with alemtuzumab. Caregivers also reported improvement in patients’ QoL over time, but the median change from baseline (physical and psychological impact scores: -10.0 and -14.8, respectively) was not statistically significant (p>0.05). Caregivers reported similar QoL and caregiver burden at baseline and EOS, apart from an increase in emotional QoL. Headache (51.2%), pyrexia (44.2%), and rash (34.9%) were the most common adverse events (AEs). Majority of the AEs were either mild or moderate, apart from 25 severe AEs. Three patients discontinued prematurely, of which one patient died of sepsis related to treatment. ConclusionThis real-world study showed beneficial impact of alemtuzumab on fatigue, cognition, depression, QoL, and treatment satisfaction. Improvement in patient disability, and caregiver-reported outcomes indicated enhanced patients’ QoL.

The Clinical Utility of the Ocrelizumab for the Patients with Multiple Sclerorsis

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory disease of the central nervous system, primarily affecting young adults, and is characterized by demyelination and neurodegeneration. Although several disease-modifying therapies (DMTs) are available in Korea, patients who experience inadequate responses or disease progression continue to require more effective and safer therapeutic options. Ocrelizumab, a humanized monoclonal antibody targeting CD20 of B cells, has shown high efficacy in both relapsing forms of multiple sclerosis and primary progressive multiple sclerosis patients. It was approved by the Food and Drug Administration in 2017 and approved by Ministry of Food and Drug Safety Korea in 2024. Clinical trials such as the OPERA and ORATORIO studies demonstrated that ocrelizumab significantly reduced relapse rates, disability progression, and magnetic resonance imaging lesions compared to interferon beta 1a or placebo. Real-world data further supports its clinical value, showing similar or superior efficacy to other high-efficacy DMTs. Long-term safety profile of ocrelizumab remains favorable, with manageable risks such as infections, particularly lower respiratory tract and urinary tract infections. This review discusses the clinical value of ocrelizumab in the treatment of multiple sclerosis, its potential as a tolerable high efficacy treatment option for patients in need of more effective therapies. Based on the clinical evidence, ocrelizumab offers a promising therapeutic opportunity for Korean MS patients, especially those with high disease activity, and is expected to become an essential part of MS treatment strategies worldwide.

The sphingosine-1-phosphate signaling pathway (sphingosine-1-phosphate and its receptor, sphingosine kinase) and epilepsy.

Epilepsy is one of the common chronic neurological diseases, affecting more than 70 million people worldwide. The brains of people with epilepsy exhibit a pathological and persistent propensity for recurrent seizures. Epilepsy often coexists with cardiovascular disease, cognitive dysfunction, depression, etc., which seriously affects the patient's quality of life. Although our understanding of epilepsy has advanced, the pathophysiological mechanisms leading to epileptogenesis, drug resistance, and associated comorbidities remain largely unknown. The use of newer antiepileptic drugs has increased, but this has not improved overall outcomes. We need to deeply study the pathogenesis of epilepsy and find drugs that can not only prevent the epileptogenesis and interfere with the process of epileptogenesis but also treat epilepsy comorbidities. Sphingosine-1-phosphate (S1P) is an important lipid molecule. It not only forms the basis of cell membranes but is also an important bioactive mediator. It can not only act as a second messenger in cells to activate downstream signaling pathways but can also exert biological effects by being secreted outside cells and binding to S1P receptors on the cell membrane. Fingolimod (FTY720) is the first S1P receptor modulator developed and approved for the treatment of multiple sclerosis. More and more studies have proven that the S1P signaling pathway is closely related to epilepsy, drug-resistant epilepsy, epilepsy comorbidities, or other epilepsy-causing diseases. However, there is much controversy over the role of certain natural molecules in the pathway and receptor modulators (such as FTY720) in epilepsy. Here, we summarize and analyze the role of the S1P signaling pathway in epilepsy, provide a basis for finding potential therapeutic targets and/or epileptogenic biomarkers, analyze the reasons for these controversies, and put forward our opinions. PLAIN LANGUAGE SUMMARY: This article combines the latest research literature at home and abroad to review the sphingosine 1-phosphate signaling pathway and epileptogenesis, drug-resistant epilepsy, epilepsy comorbidities, other diseases that can cause epilepsy, as well as the sphingosine-1-phosphate signaling pathway regulators and epilepsy, with the expectation of providing a certain theoretical basis for finding potential epilepsy treatment targets and/or epileptogenic biomarkers in the sphingosine-1-phosphate signaling pathway.

Ocrelizumab in Early-Stage Relapsing-Remitting Multiple Sclerosis: The Phase IIIb ENSEMBLE 4-Year, Single-Arm, Open-Label Trial.

Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS). ENSEMBLE was a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. Patients were treatment naive, aged 18-55 years, had early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) score ≤3.5, and ≥1 clinically reported relapse(s) or ≥1 signs of brain inflammatory activity on MRI in the prior 12 months. Patients received IV ocrelizumab 600 mg every 24 weeks. Effectiveness endpoints over 192 weeks were proportion of patients with no evidence of disease activity (NEDA-3; defined as absence of relapses, 24-week confirmed disability progression [CDP], and MRI measures, with prespecified MRI rebaselining at week 8), 24-week/48-week CDP and 24-week confirmed disability improvement, annualized relapse rate (ARR), mean change in EDSS score from baseline, and safety. Cognitive status, patient-reported outcomes, and serum neurofilament light chain (NfL) were assessed. Descriptive analysis was performed on the intention-to-treat population. Baseline characteristics (N = 678) were consistent with early-stage RRMS (n = 539 patients, 64.6% female, age 40 years and younger; median age: 31.0 years; duration since: MS symptom onset 0.78 years, RRMS diagnosis 0.24 years; mean baseline EDSS score [SD] 1.71 [0.95]). At week 192, most of the patients had NEDA-3 (n = 394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027). NfL levels were reduced to and remained within the healthy donor range, by week 48 and week 192, respectively. No new or unexpected safety signals were observed. Disease activity based on clinical and MRI measures was absent in most of the patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab. Although this single-arm study was limited by lack of a parallel group for comparison of outcome measures, the positive benefit-risk profile observed may provide confidence to adopt ocrelizumab as a first-line treatment in newly diagnosed patients with early RMS. This study provides Class IV evidence that adult patients with early-stage MS who were treatment naive maintained low disease activity (NEDA-3) over 4 years with ocrelizumab treatment; no new safety signals were detected. ClinicalTrials.gov Identifier NCT03085810; first submitted March 16, 2017; first patient enrolled: March 27, 2017; available at clinicaltrials.gov/ct2/show/NCT03085810.

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical. This topic was discussed during an international focused workshop organized by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in 2023. The aim was to review the current evidence on the rationale for, but also the potential pitfalls of, treatment de-escalation in MS. Several clinical scenarios emerged, mainly driven by a change in the benefit-risk ratio of DMTs over the course of the disease and with aging. The workshop also addressed the issue of de-escalation by the type of DMT used and in specific situations including pregnancy and paediatric onset MS. Finally, we provide practical guidelines for selecting appropriate patients, defining de-escalation and monitoring modalities, and outline unmet needs in this field.

Improvements in quality of life of patients with multiple sclerosis receiving alemtuzumab in clinical practice: the LEMVIDA study

BackgroundAlemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Its efficacy and safety have been widely demonstrated in clinical trials, but experience from real-world cohorts is also needed to support its clinical use. Quality of life (QoL) outcomes are an important complement to the clinical benefits of treatment, offering a patient-centered perspective on how the drug contributes to general well-being. In this line we aimed to evaluate the QoL of patients treated with alemtuzumab in clinical practice.MethodsThis prospective 3-year multicenter study was carried out in adult patients diagnosed with RRMS who had started alemtuzumab according to clinical practice within 8 weeks before inclusion. The primary endpoint was the change in QoL over three years of treatment with alemtuzumab using the 29-item Multiple Sclerosis Impact Scale (MSIS-29). Secondary endpoints included changes from baseline in the 21-item Modified Fatigue Impact Scale (MFIS-21), Beck Depression Inventory (BDI-II), Symbol Digit Modalities Test (SDMT, oral version) and Work Productivity. Disability worsening was also assessed based on the Expanded Disability Status Scale (EDSS), along with the annualized relapse rate (ARR) and radiological activity.ResultsA cohort of 165 patients was analyzed (mean age 38.6 years, mean disease duration 8.5 years, mean EDSS score 3.3). MSIS-29 physical domain scores decreased significantly from baseline by a mean of 7.2 ± 1.8 points at year 1, 6.4 ± 2.2 at year 2 and 5.6 ± 2.3 at year 3 (p < 0.05 in all cases). Similarly, MSIS-29 psychological domain scores decreased significantly by a mean of 7.9 ± 2.4 points at year 1, 12.8 ± 2.9 at year 2 and 13.2 ± 3.0 at year 3 (p < 0.05 in all cases). Significant reductions from baseline were also evidenced in MFIS-21 and BDI-II scores, while SDMT scores remained unchanged. During the 3 years on alemtuzumab, the ARR was 0.15, representing an 83% reduction from the 2 years before initiation. At 3 years, 81.5% of patients were free from radiological activity and 87% were free from disability worsening.ConclusionsThese results indicate early and substantial improvements in patients’ perception of their QoL and functioning with alemtuzumab that were sustained over three years.

Comparison of intravenous and subcutaneous administration of ocrelizumab. Time and motion study

Introduction and objective: Ocrelizumab is used in multiple sclerosis treatment and is available in intravenous and subcutaneous forms. In Poland, only the intravenous form is currently reimbursed. The subcutaneous form offers a shorter administration time, potentially benefiting both healthcare providers and patients. This study evaluates the impact of the different forms of ocrelizumab administration on medical facility workflow and costs. Materials and methods: A survey was conducted in six medical centres involving 329 patients treated with ocrelizumab in 2023, with 46 patients receiving the subcutaneous form of the drug. The study assessed the complete drug administration process, including premedication, preparation, administration, and post-administration observation. The comparison between the two forms of ocrelizumab focused on the costs associated with drug administration, the time patients spent at the medical centre, and the efficiency of the drug administration process. Results: The administration costs of the subcutaneous form were significantly lower (96.80 PLN) than the intravenous form (224.32 PLN). The time patients spent at the medical centre was greatly reduced for the subcutaneous form (56 minutes) compared to the intravenous form (242 minutes). Efficiency in drug administration was also higher for the subcutaneous (26.88) than the intravenous form (2.62). Conclusions: The study highlights the substantial benefits of the subcutaneous form of ocrelizumab over the intravenous form. These advantages are noticeable from both the healthcare provider’s and patient’s perspectives, underscoring the potential for improved efficiency and patient experience with the subcutaneous form.

Experience with the long-term use of interferons β in the treatment of relapsing-remitting multiple sclerosis. Case report

Current approaches to treating multiple sclerosis aim at controlling disease activity. Despite the variety of agents that have proven their effectiveness and were introduced in practice in the last decade, the use of the interferon β group remains relevant. The article presents clinical cases of long-term use of interferons β in treating multiple sclerosis.

Family planning and contraception in people with multiple sclerosis: perspectives for obstetricians, gynaecologists, and other health care professionals involved in reproductive planning.

Multiple sclerosis (MS) is often diagnosed in people of reproductive age. However, family planning counselling is not always integrated within MS care. Decisions on family planning can be further complicated by potential side effects associated with several disease-modifying therapies. While neurologists may lack training in contraceptive use and family planning counselling, obstetricians and gynaecologists (OB-GYNs) and other health care professionals involved in reproductive life planning (RHCPs) may lack detailed knowledge and experience around the use of contemporary MS treatments. Through a modified Delphi consensus programme, a multidisciplinary steering committee of 13 international experts developed practical clinical recommendations on contraceptive use and family planning for people with MS (PwMS). This article offers insights to help OB-GYNs and RHCPs implement these recommendations, focusing on contraceptive decision-making and MS medications. The perspectives discussed emphasise providing education on MS to OB-GYNs and other RHCPs, enabling informed counselling for PwMS and their partners regarding contraception and family planning. Close collaboration among the multidisciplinary team, including neurologists, is crucial in providing reproductive care for PwMS. The detailed perspectives provided aim to enable OB-GYNs and other RHCPs to provide informed counselling for PwMS and their partners regarding contraception and family planning.

Effects of systemic fingolimod treatment on anterior segment parameters and tear film functions

Purpose To investigate the potential effects of systemic fingolimod treatment on parameters of the anterior segment of the eye and tear film function tests in patients with multiple sclerosis (MS). Methods Forty-eight eyes of 24 individuals who were started on systemic fingolimod treatment for relapsing-remitting MS were prospectively enrolled in this study. Patients underwent examinations immediately before initiation of systemic fingolimod treatment, and at the first and sixth months of treatment. Anterior segment parameters were measured using Sirius Topography. The Schirmer-I test and tear break-up time (TBUT) were recorded during follow-up. Retinal thickness was also analyzed using spectral-domain optical coherence tomography (SD-OCT). Results There was no statistically significant difference in retinal thickness measurements between follow-up visits. The central corneal thickness, keratometric values, anterior chamber depth, aqueous humor depth, iridocorneal angle, horizontal anterior chamber tilt and anterior chamber volume values remained similar during follow-up. The Schirmer-I test value was 15.10 ± 2.65 mm at the zeroth month and 17.03 ± 3.61 mm at the sixth month (p = 0.044). The mean TBUT was significantly higher at the six-month visit compared to baseline and the one-month visit (p 0–6 < 0.001, p 1–6 < 0.001), but there was no statistically significant difference between baseline and month 1 (p 0–1 = 0.419). Conclusion Systemic use of fingolimod may increase Schirmer I test and TBUT values in MS patients without altering other anterior segment parameters within 6 months.

Unveiling preferences in multiple sclerosis care: insights from an Italian discrete-choice experiment with patients and healthcare professionals

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, neurodegenerative disease of the central nervous system, significantly impacting patients’ quality of life. Understanding patient and healthcare professional (HCP) preferences for MS treatments is crucial for optimizing therapeutic strategies and improving adherence and outcomes. This Discrete-Choice Experiment (DCE) assesses preferences for various MS treatment attributes among Italian patients and HCPs. The sample included 1069 patients and 186 HCPs. Key attributes evaluated were treatment administration route, frequency, location, and Patient-Reported Outcome Measures (PROMs), such as cognitive impairment, fatigue, and mobility. Data were collected through questionnaires and responses were analyzed to determine the relative importance (RI) and utility of each attribute. Both patients and HCPs highly prioritized PROMs, with cognitive impairments and walking ability being the most critical factors. Patients showed a strong preference for oral administration and treatments administered biannually at home, whereas HCPs preferred hospital-based treatments. The “Time to Progression” attribute was more significant for HCPs than for patients, reflecting different priorities between the groups. The study highlighted the importance of treatment convenience, with patients favoring less-frequent administration schedules and home-based treatment options. This study underscores the necessity of incorporating both patient and HCP perspectives into MS treatment planning. Shared decision-making, which considers individual preferences, can enhance treatment adherence and outcomes. These insights into treatment preferences provide valuable guidance for personalized MS care, aiming to improve patient quality of life and optimize therapeutic efficacy.

Neuroprotective and Anti-Inflammatory Effects of Dimethyl Fumarate, Monomethyl Fumarate, and Cannabidiol in Neurons and Microglia.

Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS) that can cross the blood-brain barrier, presenting neuroprotective potential. Its mechanism of action is not fully understood, and there is a need to characterize whether DMF or its bioactive metabolite monomethyl fumarate (MMF) exerts neuroprotective properties. Moreover, the combination of adjuvant agents such as cannabidiol (CBD) could be relevant to enhance neuroprotection. The aim of this study was to compare the neuroprotective and immunomodulatory effects of DMF, MMF, and CBD in neurons and microglia in vitro. We found that DMF and CBD, but not MMF, activated the Nrf2 antioxidant pathway in neurons. Similarly, only DMF and CBD, but not MMF, prevented the LPS-induced activation of the inflammatory pathway NF-kB in microglia. Additionally, the three drugs inhibited the production of nitric oxide in microglia and protected neurons against apoptosis. Transcriptomically, DMF modulated a greater number of inflammatory and Nrf2-related genes compared to MMF and CBD in both neurons and microglia. Our results show that DMF and MMF, despite being structurally related, present differences in their mechanisms of action that could be relevant for the achievement of neuroprotection in MS patients. Additionally, CBD shows potential as a neuroprotective agent.

Ozanimod in Relapsing Multiple Sclerosis: New Insights

Ozanimod is an approved treatment for relapsing forms of multiple sclerosis (RMS) that has been shown to reduce relapses, new brain lesions, and brain volume loss relative to intramuscular interferon (IFN) β-1a. This article summarizes selected data from clinical trials of ozanimod in RMS, which were presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) held in Denmark in September 2024 and the Annual Meeting of the European Charcot Foundation held in Italy in November 2024. Final safety data were presented for the completed open-label extension (OLE) study of ozanimod in adults with RMS (DAYBREAK), showing that rates of adverse events (AE) remained stable or decreased over 8 years of ozanimod treatment. These findings confirm the established safety profile of ozanimod. An analysis of brain volume changes across DAYBREAK and parent trials were also presented, demonstrating that the annualized rate of brain volume loss in participants treated with continuous ozanimod for up to 7 years was below the pathologic cutoff and was similar to those previously reported from healthy controls. Data were presented from a retrospective, observational study into the effects of switching from fingolimod to ozanimod in patients with RMS due to safety or intolerance reasons. The authors concluded that this study confirms that switching from fingolimod to ozanimod for safety reasons such as lymphopenia or hypertransaminasemia may be a good strategy to continue sphingosine-1-phosphate receptor (S1PR)-modulating drug therapy. Finally, an ad hoc interim analysis of patients with early RMS from ENLIGHTEN showed promising results, demonstrating that more than three-quarters of patients had either stable or improved cognitive processing speed after 1 year of ozanimod 0.92 mg.

59. Patient Perspectives and Nursing Satisfaction in the Evaluation of High Efficacy Treatment in Multiple Sclerosis: A Cross-sectional Study

59. Patient Perspectives and Nursing Satisfaction in the Evaluation of High Efficacy Treatment in Multiple Sclerosis: A Cross-sectional Study

70. Real-World Experience of Cladribine Tablets in the Treatment of Multiple Sclerosis: An Omani Cohort from Khoula Hospital

70. Real-World Experience of Cladribine Tablets in the Treatment of Multiple Sclerosis: An Omani Cohort from Khoula Hospital

EE358 Systematic Literature Review on Economic Evaluations of Disease-Modifying Treatments in Multiple Sclerosis: Current Insights and Future Directions

EE358 Systematic Literature Review on Economic Evaluations of Disease-Modifying Treatments in Multiple Sclerosis: Current Insights and Future Directions