Management Of Multiple Sclerosis Research Articles

Current and future trends in multiple sclerosis management: Near East perspective.

Multiple sclerosis (MS) prevalence is rising in the Middle East. Most MS medications are available in the region, but not all, possibly affecting neurologists' prescribing habits. To provide an overview of the current practices of Near East (NE) healthcare practitioners by probing their prescribing decisions, to report the COVID-19 impacts on neurologists' prescribing habits, and to explore the future relevance of current medication used in MS management among other newcomers. A cross-sectional study was carried out using an online survey from April 27, 2022, to July 5, 2022. The questionnaire was designed with the input of five neurologists representing five NE countries (Iran, Iraq, Lebanon, Jordan & Palestine). They identified several factors that play a crucial role in the optimal care of MS patients. The link was shared among neurologists using snowball sampling. The survey included 98 neurologists. Effectiveness and safety balance was the most important factor considered when selecting the MS treatment. Among patients with MS, the most challenging factor for the patients was thought to be related to family planning, followed by affordability and tolerability of side effects. In the treatment of mild to moderate relapsing remitting multiple sclerosis (RRMS) in men, Interferon beta 1a SC, Fingolimod, and Glatiramer acetate were the most commonly recommended treatments. Dimethyl fumarate substituted fingolimod in female patients. Interferon beta 1a SC was the safest treatment for mild to moderate RRMS. Interferon beta 1a SC was preferred over other treatments for patients with mild to moderate MS and planning for pregnancy (56.6%) or breastfeeding (60.2%). Fingolimod was not a choice for these patients. Neurologists seemed to discuss the top three treatments of Natalizumab, Ocrelizumab, and Cladribine with patients with highly active MS. When asked to position future disease-modifying therapies five years from today, more than 45% of physicians expressed a lack of information on Bruton's tyrosine kinase (BTK) inhibitors. Most neurologists in the NE region followed Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) recommendations for prescribing treatment. The treatment choice also depended on the availability of disease-modifying therapies (DMTs) in the region. Regarding the use of upcoming DMTs, there is a clear need for real-world data, long-term extension studies, and comparative studies to support their efficacy and safety profiles in treating patients with MS.

“Effect of incorporating a molten salt waste from nuclear power plants on the properties of geopolymers and Portland cement wasteforms”

This research studies the effect of incorporating a surrogate molten salt radioactive waste (labelled as MS, composed of a mixture of carbonates, chlorides and sulphates) on the mechanical, mineralogical and microstructural features of two types of cementitious systems: i) Portland cementitious systems and ii) a novel “one-part geopolymer”. As Portland cementitious systems, a CEM I/42.5 SR and a CEM III/B 32.5, were selected. The “one-part” geopolymer was prepared with mixtures of metakaolin and blast furnace slag as precursors, and NaOH and Na2SiO3 powders, as solid activators. Results shown that the MS interacts with both cementitious matrixes, affecting the hydration/activation and promoting the crystallisation of sodium/calcium carbonate hydrated phases. Mechanical strengths substantially declined and the microstructure was clearly affected, especially in samples containing 30% of the MS. Some lines of action are suggested to improve the cementation treatment of MS minimising its effect in the development of the different cementitious materials.

Engagement with three or more healthy lifestyle behaviours is associated with improved quality of life over 7.5 years in people with multiple sclerosis.

People with multiple sclerosis (pwMS) report reduced quality of life (QoL). Engagement with healthy lifestyle behaviours, including consuming a healthy diet, regular physical activity, and adequate vitamin D exposure, is associated with higher QoL. We aim to assess whether individual lifestyle behaviours are more beneficial to QoL than others, and whether there are additive benefits to QoL by engaging in multiple healthy behaviours concurrently. Data from pwMS who completed an online survey at baseline, and at 2.5-, 5- and 7.5-year follow-up, were analysed. Behaviours assessed were consumption of a no-meat/dairy-plus-omega-3 supplementation diet, meditation practice, physical activity, non-smoking, and vitamin D exposure. Mental QoL (mQoL) and physical QoL (pQoL) were assessed by the Multiple Sclerosis Quality of Life (MSQOL-54) questionaire. Linear regression analyses were performed to assess associations of individual behaviours at baseline and follow-up time points with QoL, as well as between number of behaviours and QoL. At baseline, healthy diet and regular physical activity were associated with higher mQoL (5.3/100 and 4.0/100) and higher pQoL (7.8/100 and 6.7/100). Prospectively, diet was positively associated with mQoL, and physical activity with both mQoL and pQoL. At baseline, engagement with ≥3 behaviours was positively associated with mQoL and pQoL, with additive positive associations for each additional behaviour. Prospectively, engagement with ≥3 behaviours was positively associated with mQoL and pQoL, with strongest associations observed with engagement with five behaviours. Consumption of a healthy diet, and regular physical activity, are both potential interventions to improve QoL. Engagement with multiple lifestyle behaviours may provide additional benefits and should be encouraged and supported for multiple sclerosis management.

Application of Desulphurized Gypsum with Straw to Improve Physicochemical Properties of Saline-alkali Land in Yellow River Delta

In order to explore the effect of combining straw and desulphurized gypsum on improving coastal saline-alkali soil, taking the alkaline saline soil in the Yellow River Delta as the research object, six treatments including the control (CK), desulphurized gypsum (DG), medium straw amount (MS), desulphurized gypsum+low straw amount (DGLS), desulphurized gypsum+medium straw amount (DGMS), and desulphurized gypsum+high straw amount (DGHS) were set up through a field location experiment. Combined with the aggregate classification method, the changes in bulk density, total porosity, pH, soluble salt content, microbial biomass carbon, dissolved organic carbon, new carbon, and aggregate organic carbon of coastal saline alkali soil under different treatments were compared. The results showed that the MS and DGHS treatments significantly reduced soil bulk density and increased soil total porosity, water content, and average weight diameter. The pH and exchange sodium percentage decreased significantly under all treatments, and there was no significant difference. DG treatment significantly reduced the soil sodium adsorption ratio. Compared with that in the MS treatment, the soil sodium adsorption ratio of DGLS, DGMS, and DGHS showed a further decreasing trend, with a decrease range of 57%-66%. Compared with MS, soil soluble Na+ decreased by 27.92%, 32.23%, and 20.15% under the DGLS, DGMS, and DGHS treatments, whereas the soil soluble Ca2+ and SO42- contents increased significantly. Compared with that in CK, all treatments could significantly reduce Cl- content, and there was no significant difference among all treatments. Compared with that in MS, microbial biomass carbon and dissolved organic carbon were significantly increased by 113% and 147% by DGMS and 22.81% and 28.24% by DGHS, respectively. The new carbon formation of DGLS, DGMS, and DGHS was 67%, 114%, and 175% higher than that of MS, respectively. The average size proportion of fine aggregates treated by DGLS, DGMS, and DGHS was 29.12% higher than that treated by MS. Straw returning and application of desulfurized gypsum increased the organic carbon content of coarse aggregates and fine aggregates in salinized soil. The average value of new carbon formation in coarse aggregates and fine aggregates treated by DGMS and DGHS was 233% and 142% higher than that treated by MS, respectively. Desulphurized gypsum applied to soil did not lead to soil heavy metal pollution, and the soil heavy metal content of different treatments was lower than the secondary standard of the soil environmental quality standard. These results can provide scientific basis for the improvement and utilization of coastal saline-alkali soil and the comprehensive utilization of industrial and agricultural wastes in the Yellow River Delta.

Magnolol as STAT3 inhibitor for treating multiple sclerosis by restricting Th17 cells

ObjectiveMultiple sclerosis (MS) is an immune disease in the central nervous system (CNS) associated with Th17 cells. Moreover, STAT3 initiates Th17 cell differentiation and IL-17A expression through facilitating RORγt in MS. Here, we reported that magnolol, isolated from Magnolia officinalis Rehd. Et Wils, was regarded as a candidate for MS treatment verified by both in vitro and in vivo studies. MethodsIn vivo, experimental autoimmune encephalomyelitis (EAE) model in mice was employed to evaluate the alleviation of magnolol on myeloencephalitis. In vitro, FACS assay was employed to evaluate the effect of magnolol on Th17 and Treg cell differentiation and IL-17A expression; network pharmacology-based study was applied to probe the involved mechanisms; western blotting, immunocytochemistry, and luciferase reporter assay was used to further confirm the regulation of magnolol on JAK/STATs signaling pathway; surface plasmon resonance (SPR) assay and molecular docking were applied to manifest affinity with STAT3 and binding sites; overexpression of STAT3 was employed to verify whether magnolol attenuates IL-17A through STAT3 signaling pathway. ResultsIn vivo, magnolol alleviated loss of body weight and severity of EAE mice; magnolol improved lesions in spinal cords and attenuated CD45 infiltration, and serum cytokines levels; correspondingly, magnolol focused on inhibiting Th17 differentiation and IL-17A expression in splenocyte of EAE mice; moreover, magnolol selectively inhibited p-STAT3(Y705) and p-STAT4(Y693) of both CD4+ and CD8+ T cells in splenocyte of EAE mice. In vitro, magnolol selectively inhibited Th17 differentiation and IL-17A expression without impact on Treg cells; network pharmacology-based study revealed that magnolol perhaps diminished Th17 cell differentiation through regulating STAT family members; western blotting further confirmed that magnolol inhibited p-JAK2(Y1007) and selectively antagonized p-STAT3(Y705) and slightly decreased p-STAT4(Y693); magnolol antagonized both STAT3 nucleus location and transcription activity; magnolol had a high affinity with STAT3 and the specific binding site perhaps to be at SH2 domain; overexpression of STAT3 resulted in failed inhibition of magnolol on IL-17A. ConclusionMagnolol selectively inhibited Th17 differentiation and cytokine expression through selectively blocking of STAT3 resulting in decreased the ratio of Th17/Treg cells for treating MS, suggesting that the potential of magnolol for treating MS as novel STAT3 inhibitor.

Clinical and economic evaluations of natalizumab, rituximab, and ocrelizumab for the management of relapsing-remitting multiple sclerosis in Saudi Arabia

IntroductionThe advent of new disease-modifying therapies (DMTs), such as monoclonal antibodies (mAbs), resulted in significant changes in the treatment guidelines for Multiple sclerosis (MS) and improvement in the clinical outcomes. However, mAbs, such as rituximab, natalizumab, and ocrelizumab, are expensive with variable effectiveness rates. Thus, the present study aimed to compare the direct medical cost and consequences (e.g., clinical relapse, disability progression, and new MRI lesions) between rituximab and natalizumab in managing relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia. Also, the study aimed to explore the cost and consequence of ocrelizumab in managing RRMS as a second-choice treatment.MethodsThe electronic medical records (EMRs) of patients with RRMS were retrospectively reviewed to retrieve the patients’ baseline characteristics and disease progression from two tertiary care centers in Riyadh, Saudi Arabia. Biologic–naïve patients treated with rituximab or natalizumab or those switched to ocrelizumab and treated for at least six months were included in the study. The effectiveness rate was defined as no evidence of disease activity (NEDA-3) (i.e., absence of new T2 or T1 gadolinium (Gd) lesions as demonstrated by the Magnetic Resonance Imaging (MRI), disability progression, and clinical relapses), while the direct medical costs were estimated based on the utilization of healthcare resources. In addition, bootstrapping with 10,000 replications and inverse probability weighting based on propensity score were conducted.ResultsNinety–three patients met the inclusion criteria and were included in the analysis (natalizumab (n = 50), rituximab (n = 26), ocrelizumab (n = 17)). Most of the patients were otherwise healthy (81.72%), under 35 years of age (76.34%), females (61.29%), and on the same mAb for more than one year (83.87%). The mean effectiveness rates for natalizumab, rituximab, and ocrelizumab were 72.00%, 76.92%, and 58.83%, respectively. Natalizumab mean incremental cost compared to rituximab was $35,383 (95% CI: $25,401.09– $49,717.92), and its mean effectiveness rate was 4.92% lower than rituximab (95% CI: -30–27.5) with 59.41% confidence level that rituximab will be dominant.ConclusionsRituximab seems to be more effective and is less costly than natalizumab in the management of RRMS. Ocrelizumab does not seem to slow the rates of disease progression among patients previously treated with natalizumab.

MS becomes a treatable disease: 30 years later

30 years ago the first disease-modifying therapy for relapsing multiple sclerosis was approved for use in the United States and soon thereafter across the globe. Since then the field of MS therapeutics, and studies of immunopathogenesis and genetics, have advanced our understanding of the disease and raised the hope of better addressing the next challenges of treating progressive disease, enhancing repair of the damaged nervous system and, hopefully, of a cure. Thirty years into the MS treatment era, the field continues to debate fundamental aspects of MS, and there exists a widening chasm between the triumphs in relapsing disease and the desolation of MS progression, which remains the principal unmet need. In this Personal Viewpoint, we outline lessons learned from the first era of great therapeutic development, as we look to the future of MS research and therapeutics.

The first factor affecting dryland winter wheat grain yield under various mulching measures: Spike number

Water is the key factor limiting dryland wheat grain yield. Mulching affects crop yield and yield components by affecting soil moisture. Further research is needed to determine the relationships between yield components and soil moisture with yield, and to identify the most important factor affecting grain yield under various mulching measures. A long-term 9-year field experiment in the Loess Plateau of Northwest China was carried out with three treatments: no mulch (CK), plastic mulch (MP) and straw mulch (MS). Yield factors and soil moisture were measured, and the relationships between them were explored by correlation analysis, structural equation modeling and significance analysis. The results showed that compared with CK, the average grain yields of MP and MS increased by 13.0 and 10.6%, respectively. The average annual grain yield of the MP treatment was 134 kg ha−1 higher than the MS treatment. There were no significant differences in yield components among the three treatments (P<0.05). Soil water storage of the MS treatment was greater than the MP treatment, although the differences were not statistically significant. Soil water storage during the summer fallow period (SWSSF) and soil water storage before sowing (SWSS) of MS were significantly higher than in CK, which increased by 38.5 and 13.6%, respectively. The relationship between MP and CK was not statistically significant for SWSSF, but the SWSS in MP was significantly higher than in CK. In terms of soil water storage after harvest (SWSH) and water consumption in the growth period (ET), there were no significant differences among the three treatments. Based on the three analysis methods, we found that spike number and ET were positively correlated with grain yield. However, the relative importance of spike number to yield was the greatest in the MP and MS treatments, while that of ET was the greatest in CK. Sufficient SWSSF could indirectly increase spike number and ET in the three treatments. Based on these results, mulch can improve yield and soil water storage. The most important factor affecting the grain yield of dryland wheat was spike number under mulching, and ET with CK. These findings may help us to understand the main factors influencing dryland wheat grain yield under mulching conditions compared to CK.

Multiple Sclerosis Disease Activity and Disability Following Cessation of Fingolimod for Pregnancy.

Discontinuation of fingolimod ≥2 months before pregnancy is recommended to minimize potential teratogenicity. The magnitude of MS pregnancy relapse risk, particularly severe relapses, after fingolimod cessation is unclear, as is whether this risk is reduced by pregnancy or modifiable factors. Pregnancies who stopped fingolimod treatment within 1 year before or during pregnancy were identified from the German MS and Pregnancy Registry. Data were collected through structured telephone-administered questionnaires and neurologists' notes. Severe relapses were defined as a ≥2.0 increase in Expanded Disability Status Scale (EDSS) or new or worsening relapse-related ambulatory impairment. Women who continued to meet this definition 1 year postpartum were classified as reaching the Severe Relapse Disability Composite Score (SRDCS). Multivariable models accounting for measures of disease severity and repeated events were used. Of the 213 pregnancies among 201 women (mean age at pregnancy onset 32 years) identified, 56.81% (n = 121) discontinued fingolimod after conception. Relapses during pregnancy (31.46%) and the postpartum year (44.60%) were common. Nine pregnancies had a severe relapse during pregnancy and additional 3 during the postpartum year. One year postpartum, 11 of these (6.32% of n = 174 with complete EDSS information) reached the SRDCS. Adjusted relapse rates during pregnancy were slightly higher compared with the year before pregnancy (relapse rate ratio = 1.24, 95% CI 0.91-1.68). Neither exclusive breastfeeding nor resuming fingolimod within 4 weeks of delivery were associated with a reduced risk of postpartum relapses. Most pregnancies relapsed during the first 3 months postpartum (n = 55/204, 26.96%). Relapses during pregnancy after fingolimod cessation are common. Approximately 6% of women will retain clinically meaningful disability from these pregnancy-related, fingolimod cessation relapses 1 year postpartum. This information should be shared with women on fingolimod desiring pregnancy, and optimizing MS treatment with nonteratogenic approaches should be discussed.

Navigating the journey of multiple sclerosis management in Africa, overcoming hurdles and harnessing opportunities: a review.

Multiple sclerosis (MS) is a chronic, debilitating condition affecting many African people. However, the management of MS in Africa is often inadequate, and there is a need to improve the care and support provided to patients. This paper aims to identify the challenges and opportunities in navigating the journey of MS management in Africa. MS management's main challenges in Africa include a lack of awareness and education about the disease, limited access to diagnostic tools and treatments, and inadequate care coordination. However, by increasing awareness and education about MS, improving access to diagnostic tools and treatments, fostering multidisciplinary collaborations, encouraging and supporting research on MS in Africa, and collaborating with regional and international organizations to share knowledge and resources, it is possible to improve the management of the disease and improve the lives of those affected by MS in Africa. This paper concludes that improving the management of MS in Africa requires a concerted effort from all stakeholders, including healthcare professionals, policymakers, and international organizations. Collaboration and sharing of knowledge and resources are crucial to ensure that patients receive the best possible care and support.

A comprehensive review on multiple sclerosis: It’s etiology, symptoms, epidemiology and current therapeutic approaches

Multiple sclerosis is a chronic autoimmune, inflammatory neurological disease affecting the nervous system. It targets the myelin sheath of the axons and inflicts axonal degeneration. High susceptibility is seen in people of age group 20-40 years. The incidence rate is three times more in females compared to males. There are 4 types of multiple sclerosis, namely relapsing/remitting multiple sclerosis, secondary progressive multiple sclerosis, primary progressive multiple sclerosis, progressive relapsing multiple sclerosis with relapsing-remitting being the predominant type and makes up 85% of the cases. The pathogenesis of multiple sclerosis includes destruction of myelin sheath followed by formation of lesions and inflammation. Environmental factors and genetic variables play major role in development of the disease. Exposure to viral and bacterial agents can also lead to multiple sclerosis. Disease-modifying therapies (DMTs) are the most commonly employed management strategies for treating patients with multiple sclerosis. Conventional drugs like IFN-β-1a and glatiramer acetate are now being replaced by highly effective DMTs and autologous hematopoietic stem cell transplantation. Recently, there has been drastic developments in the management of multiple sclerosis, owing to the discovery of more tailored and individualized treatment protocols catering specifically to patient needs.

Using Plasma NfL and GFAP to Monitor Response to Anti-CD20 Treatment in MS (P1-3.010)

<h3>Objective:</h3> To compare changes in plasma concentrations of Neurofilament light (NfL) and Glial Fibrillary Acidic Protein (GFAP) in individuals with relapsing multiple sclerosis (RMS) vs progressive multiple sclerosis (PMS), treated with anti-CD20 immunotherapy (rituximab or ocrelizumab) <h3>Background:</h3> Blood biomarkers, especially NfL, can augment clinical and radiographic data in MS treatment monitoring. Few studies have investigated longitudinal change in NfL or GFAP in PMS patients taking anti-CD20s or compared changes in these biomarkers between RMS and PMS. <h3>Design/Methods:</h3> Subjects were selected by MS diagnosis, anti-CD20 treatment for at least 6 months, and presence of multiple blood samples in our Center’s Biorepository. Demographic/clinical information was extracted by chart review. SIMOA plasma assays of NfL and GFAP were conducted at baseline and follow-up (between 3 and 12 months) on Quanterix SR-X. Biomarker concentrations were log transformed. Summary statistics and longitudinal regression analyses, correcting for age, were generated. <h3>Results:</h3> 37 subjects and 67 samples were analyzed (n=7 had no follow-up samples between 3 and 12 months). 64.9% were female. RMS (n=19) had mean(SD) age 38.7(9.2). PMS (n=18) had mean age 56.1(10.4). Age-adjusted mean concentrations of NfL and GFAP did not differ significantly between RMS and PMS at baseline. Geometric mean NfL declined between baseline (6.8, 95%CI 4.2–11.0) and follow-up (4.9, 95%CI 3.3–7.3) in RMS but stayed stable in PMS. Geometric mean GFAP increased between baseline (52.4, 95%CI 35.2–77.9) and follow-up (60.8, 95%CI 40.4–91.4) in PMS but stayed stable in RMS. The changes for both NfL and GFAP differed statistically significantly between MS types. <h3>Conclusions:</h3> With anti-CD20 treatment, plasma NfL levels decreased in RMS by 27.6% while staying stable in PMS; GFAP levels increased in PMS by 16% while remaining stable in RMS. Results correlate with clinical evidence showing greater benefit of anti-CD20 immunotherapy in RMS compared to PMS. Future studies will include more subjects, longer observation, and different immunotherapies. <b>Disclosure:</b> Dr. Gross has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for AP Expert Group. The institution of Stefan Sillau has received research support from Alzheimer’s Association. The institution of Stefan Sillau has received research support from Hewitt Family Foundation; State of Colorado. The institution of Stefan Sillau has received research support from PCORI. The institution of Stefan Sillau has received research support from NINR. The institution of Stefan Sillau has received research support from Michael J. Fox Foundation. The institution of Stefan Sillau has received research support from Department of Defense. The institution of Stefan Sillau has received research support from Colorado Department of Public Health and Environment. The institution of Stefan Sillau has received research support from Benign Essential Blepharospasm Research Foundation. Stefan Sillau has a non-compensated relationship as a Statistician with Novartis that is relevant to AAN interests or activities. Stefan Sillau has a non-compensated relationship as a Statistician with Biogen that is relevant to AAN interests or activities. Sean Selva has nothing to disclose. Mrs. Ritchie has nothing to disclose.

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

Real-world effectiveness of switching treatment after initial platform injectable disease-modifying therapies in pediatric multiple sclerosis in the US (P14-3.008)

Real-world effectiveness of switching treatment after initial platform injectable disease-modifying therapies in pediatric multiple sclerosis in the US (P14-3.008)

Low Disease Activity Over 4 Years of Ocrelizumab Therapy in Treatment-Naive Patients With Early-Stage Relapsing-Remitting Multiple Sclerosis; the Phase IIIb ENSEMBLE Study (S46.004)

Low Disease Activity Over 4 Years of Ocrelizumab Therapy in Treatment-Naive Patients With Early-Stage Relapsing-Remitting Multiple Sclerosis; the Phase IIIb ENSEMBLE Study (S46.004)

Virtual Management of Multiple Sclerosis: Providing Access or Just Phoning it in?

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Effectiveness and safety profile of cladribine in an Italian real-life cohort of relapsing–remitting multiple sclerosis patients: a monocentric longitudinal observational study

IntroductionCladribine is approved for the treatment of active relapsing MS (RRMS), but its positioning in MS therapeutic scenario still needs to be fully elucidated.MethodsThis is a monocentric, observational, real-world study on RRMS patients treated with cladribine. Relapses, magnetic resonance imaging (MRI) activity, disability worsening, and loss of no-evidence-of-disease-activity-3 (NEDA-3) status were assessed as outcomes. White blood cell, lymphocyte counts and side effects were also evaluated. Patients were analyzed overall and in subgroups according to the last treatment before cladribine. The relationship between baseline characteristics and outcomes was tested to identify predictors of response.ResultsAmong the 114 patients included, 74.9% were NEDA-3 at 24 months. We observed a reduction of relapses and MRI activity, along with a stabilization of disability. A higher number of gadolinium-enhancing lesions at baseline was the only risk factor for loss of NEDA-3 during follow-up. Cladribine was more efficacious in switchers from first-line therapies or naïves. Grade I lymphopenia was more frequent at month 3 and 15. No grade IV lymphopenia cases were observed. Independent predictors of grade III lymphopenia were a lower baseline lymphocyte count and a higher number of previous treatments. Sixty-two patients presented at least one side effect and globally 111 adverse events were recorded, none of them was serious.ConclusionsOur study confirms previous data on cladribine effectiveness and safety. Cladribine is more effective when placed early in the treatment algorithm. Real-world data on larger populations with longer follow-up are needed to confirm our findings.

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

Multiple Sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system. It is a complex and heterogeneous disease, and its pathogenesis is still not completely understood. Precision medicine, which involves the use of advanced technologies such as genomics, proteomics, metabolomics, and imaging to identify specific biomarkers and disease subtypes, is a promising approach to the management of multiple sclerosis. Precision medicine in MS includes the development of targeted therapies that aim to modulate specific immune pathways involved in MS pathogenesis. This review article aims to provide an overview of the current status and future directions of precision medicine in MS. The article discusses the importance of precision diagnostics in MS, including the identification of biomarkers and imaging techniques for MS, as well as the challenges and opportunities of personalized treatment in MS. Targeted therapies in MS are also discussed, including the challenges of developing and implementing these therapies. The article highlights the potential of combination therapies in MS, and the role of AI and ML in improving biomarker identification. The challenges of implementing precision medicine in clinical practice are also addressed, including the standardization of diagnostic criteria and treatment guidelines, and the ethical and legal considerations of personalized treatment. Overall, precision medicine represents a promising approach to the management of MS, with the potential to improve diagnosis, prognosis, and treatment outcomes. However, the implementation of precision medicine in MS clinical practice requires addressing several challenges, including the standardization of diagnostic criteria and treatment guidelines, and the development of affordable and accessible technologies and therapies. With continued research and advances in technology, precision medicine has the potential to transform the field of MS research and clinical practice.

Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD.

Ocrelizumab and rituximab are monoclonal antibodies targeting the CD20 marker on B lymphocytes. The enhanced efficacy of B lymphocyte depleting therapies poses a greater risk of decreased immunoglobulin (Ig) levels. The rate and risk factors of hypogammaglobulinemia in MS and NMOSD patients treated with anti-CD20 therapies are unknown. A retrospective study was conducted among patients who received anti-CD20 therapy for the treatment of MS, NMOSD, and other related neurological disorders. The goal was to determine the incidence and risk factors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab versus rituximab. The secondary goals were to determine the rates of lymphopenia, neutropenia, and early B cell repopulation among patients on anti-CD20 therapy. Overall, 184 patients (mean age 48.4±13.7, 66.8% female) met inclusion criteria; 152 patients received ocrelizumab and 32 patients received rituximab. A total of 22 patients (12%) developed hypogammaglobulinemia. Patients who developed hypogammaglobulinemia were more likely to have been ≥50years of age (p=.0275) with lower baseline IgG (p=.001) and IgA (p=.0038) levels. Serious infections were observed in 21 patients (11%) and seen more commonly in those that developed total lymphopenia (<1.0×109/L) and had longer duration of B-cell therapy. Multivariate analysis identified age≥50years, white race, and rituximab as independent predictors of hypogammaglobulinemia, and absolute lymphopenia as an independent risk factor for serious infections. Among patients receiving anti-CD20 therapy, 12% of patients experienced hypogammaglobulinemia which was seen more commonly in white patients, at least 50years old, with lower baseline IgG and IgA levels and in those treated with rituximab. Serious infections were seen more commonly in patients with total lymphopenia and longer exposure to anti-CD20 therapy.

Saudi Consensus Recommendations on the Management of Multiple Sclerosis: Family Planning within the Management of MS

This review article addresses the complex issues faced by individuals with Multiple Sclerosis (MS) who are planning a family, becoming pregnant, or wishing to breastfeed their baby. Recommendations and guidelines were discussed and agreed upon by neurologists, neuroradiologists, nurses, and pharmacists involved in the management of MS in the Kingdom of Saudi Arabia (KSA). MS itself does not harm a pregnancy, and people with MS of childbearing age can be encouraged to enjoy family life. Family planning should be a part of the initial conversation with a newly diagnosed patient of childbearing age. Interferons and glatiramer acetate can be continued throughout pregnancy and can be administered during breastfeeding if the benefits outweigh the risks. These DMTs may be considered for a woman with well-controlled MS who is planning a pregnancy or otherwise not using contraception, according to an individualized risk-benefit analysis. The use of contraception should be maintained during the administration of other disease-modifying therapies (DMTs). Natalizumab can be administered at a reduced administration frequency to women with high MS disease activity up to 30 weeks gestation (this agent may induce hematological abnormalities in the fetus). Other DMTs should be withdrawn for variable periods before contraception is stopped and immediately after the discovery of a pregnancy (beware of rebound disease activity after withdrawing natalizumab or fingolimod). Resumption of treatment should not be delayed in women at risk of relapse during the postpartum period and especially in those who do not wish to breastfeed.