Management Of Multiple Sclerosis Research Articles

Ocrelizumab and ofatumumab comparison: an Italian real-world propensity score matched study.

The management of Multiple Sclerosis (MS) has undergone transformative evolution with the introduction of high-efficacy disease-modifying therapies (DMTs), specifically anti-CD20 monoclonal antibodies, such as ocrelizumab (OCR) and ofatumumab (OFA). This is an independent retrospective cohort study in Relapsing MS (RMS) patients followed at eight Italian MS centers who initiated treatment with OCR or OFA in the participating centers and with at least 12months on therapy. A generalized linear regression model inverse probability of treatment weight (IPTW) PS-adjusted was performed to evaluate the relationship between annualized relapse rate (ARR) and treatment groups. No evidence of disease activity-NEDA-3 at 12-month score was also collected. Safety profile of the investigated DMTs was recorded. A total cohort of 396 RMS patients fulfilled the required criteria and were enrolled in the study. Out of them, 216 had a prescription of OCR and 180 of OFA. The mean follow-up was 13.2 ± 1.9months. The estimated means for ARR did not show differences between the two groups, 0.059 for patients on OCR and 0.038 for patients on OFA (p = 0.185). The generalized regression model IPTW PS-adjusted did not reveal differences between patients on OCR and OFA (ExpBOFA 0.974, 95%CI 934-1.015, p = 0.207). NEDA-3 at 12months was experienced by 199(92.1%) patients on OCR and 170(94.4%) patients on OFA (p = 0.368). Generally, both therapies exhibit good tolerability. The treatment with OCR and OFA resulted in comparable control of disease activity with good safety profile. Our results need further validation in larger multicentre studies with long-term follow-up.

Management of multiple sclerosis in older adults: review of current evidence and future perspectives.

The prevalence of multiple sclerosis (MS) and aging MS patients is increasing worldwide. There is a need to better understand this MS sub-population, which historically is underrepresented in the literature. This narrative review examines the evolving demographics, disease course, and treatments for older adults with MS (OAMS) to address current knowledge gaps and highlight areas critical for future research. OAMS populations require special consideration by clinicians. Older individuals have different care needs than individuals with adult onset MS who are mid-life or younger. Comorbidities, an aging immune system, increasing neurodegeneration, decreasing neurologic reserve, changing benefit/risk relationship for disease modifying therapies (DMTs), and wellness require special attention to provide holistic comprehensive care. Active areas of research include potential cessation of DMTs and novel disease targets. This review highlights both the current knowledge and information gaps in the literature that are critical to understanding and properly managing OAMS. The aims are to inform MS clinicians in their current practice, as well as inspire future studies which are critical to providing quality and evidence-based care for OAMS.

Is disease-modifying therapy use in multiple sclerosis a risk factor during the COVID-19 pandemic? A large cohort study

Objective: This study aims to investigate the relationship between disease-modifying therapies (DMTs) used in people with MS (pwMS) and the risk of COVID-19 infection. Methods: This longitudinal cohort study included the MS cohort of 3402 people followed for COVID-19 infection. The whole MS cohort was interviewed at least once for information about COVID-19. A semi-structured interview was developed and performed by a team consisting of a medical doctor, nurse, and physiotherapist. Clinical information was obtained from the patient's medical records. This study was approved by the Noninvasive Research Ethics Board (Date: 08.09.2021, Decision No: 2021/25-06). Results: Of the 487 pwMS infected with COVID-19, 35 reported reinfections. The major differences regarding DMT between pwMS with and without COVID-19 infection were observed for fingolimod, ocrelizumab, and azathioprine. Forty-three (8.9%) people experienced the COVID-19 infection severely or critically; 12 (37.5%) had MS treatment with ocrelizumab. Fifty percent of pwMS who were treated in intensive care (7/14 patients) and died (3/6 patients) were being treated with ocrelizumab. As a result of regression analysis, being younger and using dimethyl fumarate, fingolimod, ocrelizumab, and cladribine DMTs were the main factors associated with having COVID-19 infection group. Conclusions: Current results show that disability due to MS and increased disease duration are not risk factors for COVID-19 infection, while age is negatively associated with contracting COVID-19 infection. These results show no relationship between the MS clinic and COVID-19 infection. We have found that using certain DMTs in pwMS increases the risk of contracting COVID-19 infection.

Unlocking Therapeutic Potential: The Role of Theta Burst Stimulation in Multiple Sclerosis Management.

Unlocking Therapeutic Potential: The Role of Theta Burst Stimulation in Multiple Sclerosis Management.

Epidemiological, Clinical, and Therapeutic Profile of Uveitis in Multiple Sclerosis: A Multicenter Study

ABSTRACT Introduction Uveitis may occur during approximately 1–3% of MS patients, corresponding to 10 times higher than in the general population. The development of uveitis is not currently considered as an inflammatory relapse of MS. There are no clinical guidelines for treating. MS with concomitant uveitis requiring systemic treatment. Purposes To analyze clinical and therapeutic characteristics of uveitis in patients with MS and the impact of MS treatment on the progression of uveitis. Materials & Methods We conducted a retrospective, observational, multicenter study in France about 54 patients. Results The form of MS most frequently associated with uveitis in our study was the relapsing-remitting form (85%). The mean time of onset of uveitis was 15 months before the diagnosis of MS. The most frequent form of uveitis was bilateral panuveitis (43%), non-granulomatous (61%), synechial (52%) and non-hypertonic (93%) with progressive onset (65%) and chronic course (66%). Conclusion MS-associated uveitis occurs most frequently before the diagnosis of relapsing-remitting MS in the form of panuveitis or intermediate uveitis, which is mildly inflammatory and whose main complications are macular edema, cataract and venous vasculitis. Despite their chronicity, these uveitis cases have a good visual prognosis and teriflunomide appears to have a positive effect on progression.

Expert teleconsultation involving patients and their primary neurologists for the management of multiple sclerosis in regions without specialists

AbstractObjectiveThis study aimed to describe the usefulness of our teleconsultation system for managing multiple sclerosis (MS) in regions without specialists.MethodsA cross‐sectional questionnaire survey involving 11 MS patients and their primary neurologists was carried out between May and December 2023. Real‐time video conferences were conducted between an MS specialist at a hub hospital and patients with their primary neurologists at one of the four regional core hospitals in Hokkaido, Japan. Patients and their primary neurologists completed questionnaires to evaluate the usefulness of the teleconsultation system.ResultsThe patients and their primary neurologists were generally satisfied with the teleconsultations and expressed willingness to continue using the system. In particular, alleviating the burden of visiting distant MS‐specialized clinics was highly appreciated by patients. In addition, patients gave high scores for questions regarding increased satisfaction with the primary neurologists' care and the treatments they offered. The primary neurologists thought the system enhanced their knowledge of MS management. However, they did not think that the system could ease their burden for managing MS patients because of challenges in time allocation and scheduling for teleconsultation sessions.ConclusionsThe present study suggested that our expert teleconsultation system for MS reduces the burden on patients of visiting distant MS‐specialized clinics, and enhances knowledge of MS management for the primary neurologists. It also promotes trust between patients and their primary neurologists, and taken together, these aspects could collectively lead to independent and sustainable MS management in regions without MS specialists.

Dilemmas and Delays: Management of Multiple Sclerosis in the Outpatient Setting (P2-6.017)

Dilemmas and Delays: Management of Multiple Sclerosis in the Outpatient Setting (P2-6.017)

Changes in Plasma NfL and GFAP in Response to Anti-CD20 Treatment in MS (P9-6.013)

Changes in Plasma NfL and GFAP in Response to Anti-CD20 Treatment in MS (P9-6.013)

Proposed Diagnostic Criteria and Management of Marburg Variant Multiple Sclerosis: A Meta-analysis (P2-6.011)

Proposed Diagnostic Criteria and Management of Marburg Variant Multiple Sclerosis: A Meta-analysis (P2-6.011)

Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review.

Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsing-remitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic.

Current and Emerging Treatment Options in Pediatric Onset Multiple Sclerosis

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, this review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Coronavirus disease 2019 infection among working-aged people with multiple sclerosis and the impact of disease-modifying therapies.

The risk of coronavirus disease 2019 among people with multiple sclerosis with different disease-modifying therapies is not well established. To investigate the occurrence of coronavirus disease 2019 and the remaining symptoms among people with multiple sclerosis and the associations with different disease-modifying therapies. Individuals aged 20-50 listed in the Swedish Multiple Sclerosis Registry were invited to participate in a survey in 2021. Information on reported coronavirus disease 2019 infection and remaining symptoms were linked to individual-level register data. The risks by disease-modifying therapy of having coronavirus disease 2019 or having remaining symptoms were estimated with logistic regression. Of the 4393 participants, 1030 (23.4%) self-reported coronavirus disease 2019 (749 confirmed and 281 suspected). The observed odds for coronavirus disease 2019 did not differ by disease-modifying therapy (p-values <0.05). The majority reporting coronavirus disease 2019 had fully recovered (68.5%), 4.2% were currently/recently sick, and 27.0% had symptoms remaining after 2 months. The most frequently reported remaining symptoms involved one's sense of smell or taste (37.0%), fatigue (20.0%), and breathing (12.0%). No statistically significant associations were observed between having remaining symptoms and the disease-modifying therapy. Despite the initial concerns of differing infection risks by MS treatments, we observed no differences in coronavirus disease 2019 occurrence or remaining symptoms among those who had coronavirus disease 2019. Nonetheless, exercising caution in interpreting our findings, it remains implicit that people with multiple sclerosis are particularly susceptible to infection and that lingering symptoms may persist beyond the initial infection.

Formulation and Evaluation of Microspheres Drug Delivery for Multiple Sclerosis Disease Condition

AMultiple sclerosis (MS) is chronic inflammatory disease that affecting the central nervous system (CNS) which leads to the degeneration of oligodendrocytes, neurons, and myelin over time. Being the foremost reason of neurological disability multiple sclerosis has affected about 2.5 million humans around the world. MS is mainly seen in early adulthood and adults in their middle age. Disease modifying agents are being used in treatment of relapsing multiple sclerosis. Medications that reduce the severity of the disease are frequently utilized as standard therapies. The immune system is the primary focus of modern MS treatments. However, researchers are putting more effort into designing novel CNS-focused treatments. Therefore, under the current scenario, an alternative route for drug delivery is required, one that provides a speedy onset of action and then maintains the drug release over an extended period. The desired prolong-acting intramuscular injecting stable fingolimod HCl microspheres to treat MS were formulated using solvent evaporation technique. Further, based on the number of factors to be optimized, formulation was prepared using solvent evaporation. Additionally, the formulated fingolimod microspheres were characterized for the size distribution of particle, particle surface morphology, and lyophilization of formulated microspheres. Post lyophilization, the formulated microspheres evaluation was done for efficiency of entrapment, drug release in-vitro, and stability parameters. Furthermore, in-vivo studies were performed on suitable animal models for the optimized formulation.

Inhibition of Epsilon Toxin-Producing Clostridium perfringens with a JuiceBased Probiotic Medical Food for Dietary Management of Multiple Sclerosis

Background Multiple sclerosis (MS) is the most common disabling neurological disease in young adults, with symptom onset generally occurring between the ages of 20 and 40 years. Worldwide, there are 2.8 million people with MS, and in the United States, nearly 1 million. Currently, nine oral medications are FDA-approved for MS, each of which has its own undesirable side effects. The root cause of MS remains unknown, but epsilon toxin-producing C. perfringens is implicated as the trigger. Proving this trigger requires the ability to eliminate the bacteria or their toxic effect. As an element of the gut microbiome, epsilon toxin-producing C. perfringens may be managed through dietary interventions, but there is no specific dietary supplement or medical food currently available for this purpose. Materials and Methods The aim of this in vitro research project was to develop a juice-based probiotic medical food for the dietary management of multiple sclerosis by inhibiting the growth of epsilon toxin-producing C. perfringens. For the probiotics, we used a proprietary blend of five strains of Bifidobacterium and ten strains of Lactobacillus (“Doctor’s Biome Signature Probiotic Blend”). For the excipient, we used a proprietary blend of organic green fruit and vegetable juices. The probiotics were added to sterilized excipient at 60 billion colony-forming units per two fluid ounces, yielding a medical food for multiple sclerosis (MF-MS). Two strains of epsilon toxin-producing C. perfringens, ATCC 3626 (type B) and ATCC 3631 (type D), were used as the target microorganisms. Results Over six days of culture, the control samples (RCM broth) showed drastic population growth of both strains, while the test samples (MF-MS) demonstrated complete inhibition of growth for both strains of epsilon toxin-producing Closterium perfringens. Conclusion We have developed a patent-pending, juice-based probiotic medical food for the dietary management of MS that inhibits the growth of both type B and type D epsilon toxin-producing Clostridium perfringens, which, according to the most recent published clinical findings, are thought to be the cause or trigger of MS. To our knowledge, this is the first in vitro study in which such an effect has been clearly demonstrated

Comparison between stem cell therapy and stem cell derived exosomes on induced multiple sclerosis in dogs

BackgroundMultiple sclerosis (MS) is a chronic condition that primarily manifests as demyelination of neuronal axons in the central nervous system, due to the loss or attack of oligodendroglia cells that form myelin. Stem cell therapy has shown promising results for the treatment of MS due to its capability to halt the immune attack, stop apoptosis and axonal degeneration, and differentiate into oligodendrocytes. Stem cell-derived Exosomes (Exosomes) have shown great capabilities for neuronal diseases as they have growth factors, complex sets of miRNA, enzymes, proteins, major peptides, lipids, and macromolecules with anti-inflammatory, angiogenesis, and neurogenesis activities.MethodsThis study aimed to compare the healing properties of stem cells, against Exosomes for the treatment of an experimentally induced MS dog model. Dog models of MS received either a single treatment of stem cells or a single treatment of Exosomes intrathecally and the treatment process was evaluated clinically, radiologically, histopathologically, and electron microscopy and cerebrospinal fluid analysis.Resultsshowed marked amelioration of the clinical signs in both treated groups compared to the control one, magnetic resonance scans showed the resolution of the hyperintense lesions at the end of the study period, the histopathology and electron microscopy showed marked healing properties and remyelination in treated groups with superiority of the stem cells compared to Exosomes.ConclusionsAlthough stem cell results were superior to Exosomes therapy; Exosomes have proven to be effective and safe important actors in myelin regeneration, and their use in diseases like MS helps to stimulate remyelination.

Early intensive versus escalation treatment in patients with relapsing-remitting multiple sclerosis in Austria.

To compare the effectiveness of early intensive treatment (EIT) versus escalation treatment (ESC) in a nationwide observational cohort of almost 1000 people with relapsing-remitting multiple sclerosis (RRMS). The EIT cohort started with alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR), or ozanimod (OZA); whereas, the ESC cohort was escalated from dimethylfumarate (DMF) or teriflunomide (TERI) to AZM, CLAD, FTY, NTZ, OCR, or OZA within the Austrian MS Treatment Registry. Patients had to stay on therapy for at least 3 months and up to 16years. The EIT cohort included 743 and the ESC cohort 227 RRMS patients. We used multinomial propensity scores for inverse probability weighting in generalized linear (GLM) and Cox proportional hazards models to correct for the bias of this non-randomized registry study. Estimated mean annualized relapse rates (ARR) were 0.09 for EIT and 0.4 for ESC patients. The incidence rate ratio (IRR) in the GLM model for relapses showed a decreased relapse probability of 78% for the EIT versus ESC cohort [IRR = 0.22, 95% CI (0.16-0.30), p < 0.001]. Analyzing the time to the first relapse by Cox regression, a hazard ratio (HR) of 0.17 [95% CI (0.13-0.22), p < 0.001] revealed a decreased risk of 83% for the EIT group. Regarding sustained Expanded Disability Status Scale (EDSS) progression for 12weeks, a HR of 0.55 [95% CI (0.40-0.76), p < 0.001] showed a decreased probability of 45% for the EIT cohort. ESC treatment after DMF and TERI revealed a higher relapse and EDSS progression probability compared to EIT in Austrian RRMS patients. Therefore, an early intensive treatment should be started in patients with an active or highly active disease course.

Physical Activity in Individuals Newly Diagnosed With Multiple Sclerosis Through the Lens of the COM-B Model.

Physical activity (PA) is a promising intervention for disease modification and symptom management in multiple sclerosis (MS); however, there is a lack of research focusing on PA behavior change interventions for persons newly diagnosed with MS. Such PA behavior change interventions should be developed based on a strong empirical foundation of understanding the behavior and its determinants (ie, what to target for changes to occur). To that end, this qualitative study examined factors explaining PA in persons newly diagnosed with MS and identified potential targets for future behavior change intervention development based on the Capability-Opportunity-Motivation-Behavior (COM-B) model. Twenty individuals diagnosed with MS within the past 2 years underwent one-on-one semistructured interviews using questions developed based on the COM-B model. Data were analyzed using reflective thematic analysis, and the identified themes were then mapped with the COM-B model. Factors explaining PA in the study sample were identified across the COM-B components. The typical factors include knowledge and skills to sufficiently engage in PA with appropriate approaches, ability to adapt and navigate through new environmental and social difficulties after diagnosis, and motivation resulting from a combination of factors, such as outcome expectation, belief of capabilities, role/identity, reinforcement, and emotions. The COM-B model was applied successfully in this study to understand PA behavior and identify potential targets for behavior change in individuals newly diagnosed with MS. Future behavior change interventions should consider addressing these factors to generate effective PA behavior change in this population.

Managing pediatric-onset multiple sclerosis in an austere setting: A case report.

Pediatric-onset multiple sclerosis (POMS) is the most common demyelinating disease in children. Patients suffer from physical disability, cognitive impairment, and psychosocial challenges. Management requires a multidisciplinary care team. Here we present a case of an 11-year-old boy with POMS who relocated to Guam prior to initiation of a disease-modifying treatment and who experienced a flare without immediate access to an MRI or a child neurologist. Care required the combined efforts of ophthalmology, pediatrics, and emergency medicine in Guam, real-time remote guidance by child neurology, and asynchronous collaboration with cardiology and child neurology. As a result, the immediate flare was accurately diagnosed and treated with steroids, the patient was started on Fingolimod, and an emergency management plan for future flares was constructed. This case illustrates the nuances of both the acute and chronic management of multiple sclerosis in a resource-limited setting and how a combination of synchronous and asynchronous telemedicine was able to achieve a satisfactory treatment plan.

Standardization of MRI in Multiple Sclerosis Management Consensus by the Czech Expert Radiology-Neurology Panel

Standardization of MRI in Multiple Sclerosis Management Consensus by the Czech Expert Radiology-Neurology Panel

Building digital patient pathways for the management and treatment of multiple sclerosis.

Recent advances in the field of artificial intelligence (AI) could yield new insights into the potential causes of multiple sclerosis (MS) and factors influencing its course as the use of AI opens new possibilities regarding the interpretation and use of big data from not only a cross-sectional, but also a longitudinal perspective. For each patient with MS, there is a vast amount of multimodal data being accumulated over time. But for the application of AI and related technologies, these data need to be available in a machine-readable format and need to be collected in a standardized and structured manner. Through the use of mobile electronic devices and the internet it has also become possible to provide healthcare services from remote and collect information on a patient's state of health outside of regular check-ups on site. Against this background, we argue that the concept of pathways in healthcare now could be applied to structure the collection of information across multiple devices and stakeholders in the virtual sphere, enabling us to exploit the full potential of AI technology by e.g., building digital twins. By going digital and using pathways, we can virtually link patients and their caregivers. Stakeholders then could rely on digital pathways for evidence-based guidance in the sequence of procedures and selection of therapy options based on advanced analytics supported by AI as well as for communication and education purposes. As far as we aware of, however, pathway modelling with respect to MS management and treatment has not been thoroughly investigated yet and still needs to be discussed. In this paper, we thus present our ideas for a modular-integrative framework for the development of digital patient pathways for MS treatment.