Active Multiple Sclerosis Research Articles

Early Onset of Action and Sustained Efficacy of MRI Outcomes During Cladribine Tablets Treatment in Highly Active Relapsing Multiple Sclerosis: Results of the 2-year MAGNIFY-MS Study (P6-3.018)

Early Onset of Action and Sustained Efficacy of MRI Outcomes During Cladribine Tablets Treatment in Highly Active Relapsing Multiple Sclerosis: Results of the 2-year MAGNIFY-MS Study (P6-3.018)

Blood Biomarker Dynamics in Highly Active Relapsing Multiple Sclerosis Patients Treated With Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study (S16.006)

Blood Biomarker Dynamics in Highly Active Relapsing Multiple Sclerosis Patients Treated With Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study (S16.006)

Changing Treatment Trends for MS Patients Recently Initiated on Their First DMT (P12-3.012)

<h3>Objective:</h3> To evaluate if disease-modify therapy (DMT) choice has changed for treatment-naïve multiple sclerosis (MS) patients from 2020–2022. <h3>Background:</h3> Cross-sectional audit of MS patients was conducted annually. Data were reviewed by an independent market intelligence agency which specializes in tracking the neurology market. <h3>Design/Methods:</h3> US neurologists (2020: N=199; 2021: N=205; 2022: N=208) completed a survey and contributed chart reviews for a retrospective, cross-sectional audit on MS patients who started their first DMT within the prior 3 months (2020: N=1,006; 2021: N=1,018; 2022: N=1,095). MS patients were analysed as a whole, as well as by physician-reported MS subtypes for relapsing-remitting MS (RRMS; N=722, N=768, N=827), active secondary progressive MS (aSPMS; N=74, N=50, N=59), and primary progressive MS (PPMS; N=92, N=69, N=72). <h3>Results:</h3> Overall use of glatiramer acetate (GA) (32% in 2020, 16% in 2022) has declined; use of fumarate agents (13%, 21%) and anti-CD20 monoclonal antibody (mAb) DMTs (13%, 21%) expanded. Interferon (13% in 2020 and 2022) and S1P receptor modulator class (12%, 14%) use has remained stable. Use of both brand (18%, 11%) and generics (14%, 6%) of GA declined. For fumarates, use has shifted from branded dimethyl fumarate (DMF; 13%, 8%) to generic DMF (0%, 6%) and diroximel fumarate (0%, 6%). For S1Ps, use has shifted from fingolimod (10%, 6%) to ozanimod (0%, 4%) and ponesimod (0%, 1%). Changes in DMT use are similar for RRMS: GA use declined (31%, 16%); fumarates (17%, 23%) and anti-CD20 mAb DMT (9%, 19%) use expanded. GA use also declined for aSPMS (30%, 7%) and PPMS (30%, 8%); anti-CD20 mAb DMT use grew for aSPMS (19%, 41%). <h3>Conclusions:</h3> DMT prescribing trends are evolving for MS patients recently initiated on their first DMT. Use of GA agents has fallen across MS subtypes, while use of the high-efficacy anti-CD20 mAb DMT class has expanded. <b>Disclosure:</b> Dr. McFadden has nothing to disclose.

Ocrelizumab and Cladribine had similar EDSS stability and safety profile in patients with highly active multiple sclerosis (P8-3.011)

<h3>Objective:</h3> To study change of disability in patients with highly-active relapsing remitting multiple sclerosis (RRMS) treated with cladribine or ocrelizumab. <h3>Background:</h3> Highly active MS patients have a higher risk of early progression. <h3>Design/Methods:</h3> This is prospective study including RRMS who were treated with cladribine or ocrelizumab and have one year follow up. Expanded disability status scale (EDSS) at initiation of treatment and at the end of observational period were reported. Confirmed disability progression (CDP) on EDSS defined as increase on the EDSS of at least 1.5 points for baseline EDSS of 0, an increase on the EDSS of at least 1 point for baseline EDSS between 1 and 5, or an increase of at least 0.5 point for a baseline EDSS at least 5.5. Improved disability was defined as any decrease in EDSS score 1 or more if baseline EDSS was 1–4.5 or 0.5 or more if EDSS was 5.0 or more. <h3>Results:</h3> Among 200 patients with highly-active MS, 72 patients received cladribine tablets and 128 received ocrelizumab infusions. Most of this cohort are females 139 (69.5%) with mean age 34.62 ±9.80 and mean disease duration 7.30 ±5.97. EDSS was stable among most of patients who received cladribine 56 (77.8%) and those who received ocrelizumab 105 (82%); P&lt;0.466.CPD was similar among patients under cladribine 5(6.9%) and those under ocrelizumab 9 (7%) ; P&lt;0.983. Improvement of disability was higher among cladribine group 11 (15.3%) compared to ocrelizumab group 14 (10.9%); P&lt;0.466. The mean EDSS score before cladribine was 1.63±1.30, whereas the mean EDSS before Ocrevus was 1.80±1.31. EDSS score remained stable under both cladribine 1.56±1.40 and under ocrelizumab 1.78±1.24. Patients reported mild adverse events in similar ratios under both cladribine and ocrelizumab (19.4%, 18% respectively, p&gt;0.850). <h3>Conclusions:</h3> Both cladribine and ocrelizumab resulted similar in terms of EDSS stability and safety profile. <b>Disclosure:</b> Dr. Alshawaf has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Al-Hashel has nothing to disclose. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, Bayer, Novartis, Merck, Roche, Sanofi. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen, Novartis, Merck, Roche, Sanofi.

African Americans with multiple sclerosis (MS) are more likely to have paramagnetic rim lesions (PRLs) compared to Caucasians (P11-3.017)

<h3>Objective:</h3> To determine the prevalence of paramagnetic rim lesions (PRLs) in African American patients with multiple sclerosis (AAwMS) compared to Caucasian (CAwMS). <h3>Background:</h3> PRLs are a subset of chronic active MS lesions with a rim of iron-laden innate immune cells and their presence has been associated with higher disability. AAwMS have been clinically observed to have higher disability and more severe symptoms as compared to other racial groups. <h3>Design/Methods:</h3> In this retrospective study of 139 AAwMS and 132 CAwMS quantitative susceptibility mapping (QSM), an MRI approach sensitive to iron, was used to identify PRLs. A linear model assessed the relationship between EDSS and race, adjusting for total lesion number (TLN), sex, age and disease duration (DD). The association of PRL per patient and race was modeled, adjusting for clinical variables and total lesions, using a zero-inflated Poisson regression. <h3>Results:</h3> The cohorts were well matched on all clinical variables and TLN. In a linear model, AAwMS had a higher EDSS (p-value &lt;0.001) with, on average, a 1.16-point higher EDSS (95% CI: [0.73, 1.60] than CAwMS. AAwMS had a mean of 1.3 (2.72) PRL whereas CAwMS had 0.82 (1.69), p=0.085. In the zero-inflated Poisson model, the log odds ratio of having no PRL was 0.53 (95% CI: [0.29, 0.97], p-value = 0.039) for AAwMS, indicating more patients have at least one PRL. In the Poisson model, only TLN (p = 0.021) and gender (p = 0.046) were found to be significant, which indicates that AAwMS were more likely to have one PRL, however among all patients with PRL, the total number of PRL did not depend on race. <h3>Conclusions:</h3> This is the first study to explore racial differences in the occurrence of chronic active lesions and provides preliminary evidence that PRL could relate to racial specific differences in disease pathology, an area which has been significantly understudied. <b>Disclosure:</b> Dr. Michaelson has nothing to disclose. Ms. Marcille has nothing to disclose. Dr. Sweeney has nothing to disclose. Dr. Kaunzner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Kaunzner has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medlearning. Jai Perumal has nothing to disclose. Dr. Nealon has nothing to disclose. Thanh Nguyen has nothing to disclose. Dr. Gauthier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gnenetech. The institution of Dr. Gauthier has received research support from Genentech.

Autologous hematopoietic stem cell transplantation in multiple sclerosis: A 20-year single center’s experience in Mexico. (P14-3.015)

<h3>Objective:</h3> To describe the clinical characteristics and clinical outcomes of AHSCT in Mexican patients. <h3>Background:</h3> Autologous Hematopoietic Stem Cell treatment (AHSCT) is an immune reconstitution treatment option for Multiple Sclerosis (MS) that has grown in clinical evidence over the last decades; detailed efficacy and safety data is still lacking, especially outcomes data from low-income countries. <h3>Design/Methods:</h3> Retrospective single-center observational study of all MS patients that underwent AHSCT in a single reference center in Mexico City from January 2000 to January 2020. <h3>Results:</h3> We identified 24 patients, of which 22 had at least one year of follow-up after AHSCT and underwent analysis for clinical outcome. The median follow-up time was 85 months (range: 12–267); with a median age of 44.0 years (IR 38–52); 62.8% (n=15) were men and 31.8% (n=7) women; 50% were secondary progressive forms of MS (SPMS), and 27.3% were relapsing-remitting MS (RRMS); 59% (n=13) met the criteria for highly active MS (HAMS). The composite score of no evidence of disease activity 3 or NEDA3 (no relapses, no new MRI lesions, and no EDSS progression) was achieved in all the patients at a 24-month follow-up and in 72.1% (n=16) of the patients at the time of the last follow up visit. Relapse-free survival at the last follow-up visit was achieved at 77.3%; MRI event-free survival at 90.9%; Expanded disability status scale score progression-free survival in 95.4%. Only one patient required the re-initiation of disease-modifying therapy. There was no treatment-related mortality. One patient was diagnosed with premature ovarian failure. <h3>Conclusions:</h3> AHSCT in Mexican MS patients is an effective and relatively safe treatment option with no mortality and can be performed with a reasonable degree of safety at experienced centers. <b>Disclosure:</b> Dr. Rodriguez Estrada has nothing to disclose. Dr. Molina Carrion has nothing to disclose.

Nose to brain delivery of ibudilast micelles for treatment of multiple sclerosis in an experimental autoimmune encephalomyelitis animal model

Multiple sclerosis is a chronic inflammatory disease of the central nervous system ultimate to neurodegeneration and demyelination. Ibudilast is a phosphodiesterase inhibitor, effective on the function of glial cells and lymphocytes, and inhibits the release of TNF-α by inflammatory cells. Dysregulation of glia is one of the most important pathological causes of MS. Therefore, ibudilast as a glial attenuator can be a useful treatment. The objective of the present study was to investigate the effect of nasal spray of polydopamine coated micelles of surfactin, a biosurfactant, loaded with ibudilast on its brain targeted delivery and effectiveness in remylination and neuroprotection in animal model of MS. In animal studies the micelles were administrated intranasally in different doses of 10, 25 and 50 mg/kg/day in C57/BL6 mice immunized by experimental autoimmune encephalomyelitis (EAE) model. The results of Luxol fast blue staining indicated increment in myelin fiber percent more significantly (p < 0.05) in the groups treated with the polydopamine coated micelles (PDAM) compared to nasal spray of free drug or oral administration. These formulations also increased expression of Mbp, Olig2 and Mog genes in the corpus callosum. These results suggest a positive outcome of polydopamine coated micelles loaded with ibudilast in active MS as an anti-inflammatory and neuroprotective agent.

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.

Early beginning of alemtuzumab: Changing the multiple sclerosis treatment paradigm. Interim analysis of the LEMVIDA study

IntroductionLEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain. MethodsThis is an interim analysis evaluating the baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria. Results161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed). ConclusionsUnlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.

Oral Cladribine Impairs Intermediate, but Not Conventional, Monocyte Transmigration in Multiple Sclerosis Patients across a Model Blood-Brain Barrier.

Multiple sclerosis (MS) is a disease in which the immune system damages components of the central nervous system (CNS), leading to the destruction of myelin and the formation of demyelinating plaques. This often occurs in episodic "attacks" precipitated by the transmigration of leukocytes across the blood-brain barrier (BBB), and repeated episodes of demyelination lead to substantial losses of axons within and removed from plaques, ultimately leading to progressive neurological dysfunction. Within leukocyte populations, macrophages and T and B lymphocytes are the predominant effectors. Among current immunotherapies, oral cladribine's impact on lymphocytes is well characterised, but little is known about its impact on other leukocytes such as monocytes and dendritic cells (DCs). The aim of this study was to determine the transmigratory ability of monocyte and DC subsets in healthy subjects and untreated and cladribine-treated relapse-remitting MS (RRMS) patients using a well-characterised model of the BBB. Peripheral blood mononuclear cells from subjects were added to an in vitro transmigration assay to assess cell migration. Our findings show that while prior treatment with oral cladribine inhibits the migration of intermediate monocytes, it has no impact on the transmigration of DC subsets. Overall, our data indicate a previously unrecognised role of cladribine on intermediate monocytes, known to accumulate in the brain active MS lesions.

Interactive statistical monitoring to optimize review of potential clinical trial issues during study conduct

BackgroundStatistical monitoring involves the review of prospective study data collected in participating sites to detect intra/inter patients and sites inconsistencies. We report methods and results of statistical monitoring in a phase IV clinical trial. MethodPRO-MSACTIVE is a study evaluating ocrelizumab in active relapsing multiple sclerosis (RMS) patients in France. Specific statistical methods (volcano plots, mahalanobis distance, funnel plot …) have been applied to a SDTM database to detect potential issues. R-Shiny application was developed to generate an interactive web application in order to ease site and/or patients identification during statistical data review meetings. ResultsThe PRO-MSACTIVE study enrolled 422 patients in 46 centers between July 2018 and August 2019. Three data review meetings were held between April and October 2019 and 14 standard and planned tests were run on study data, with a total of 15 (32.6%) sites identified as needing review or investigation. Overall 36 findings were identified during the meetings: duplicate records, outliers, inconsistent delays between dates. ConclusionStatistical monitoring is useful to identify unusual or clustered data patterns that might be revealing issues that could impact the data integrity and/or may potentially impact patients’ safety. With anticipated and appropriate interactive data visualization, early signals can easily be identified or reviewed by the study team and appropriate actions be set up and assigned to the most appropriate function for a close follow-up and resolution. Interactive statistical monitoring is time consuming to initiate using R-Shiny, but is time saving after the 1st data review meeting (DRV).(ClinicalTrials.gov identifier: NCT03589105; EudraCT identifier: 2018-000780-91)

Results of treatment with alemtuzumab in a Spanish cohort of patients with multiple sclerosis in the real world: The RealMS study.

Alemtuzumab (ALZ) is a humanized monoclonal antibody approved for the treatment of patients with highly active relapsing-remitting multiple sclerosis (RRMS) administered in two annual courses. The objective of this study was to describe the effectiveness and safety data of ALZ and to report the health resource utilization in patients receiving this treatment. In this retrospective, non-interventional study, information was retrieved from patients' medical charts at one center in Spain. Included patients were ≥18 years old, and ALZ treatment was initiated between 1 March 2015 and 31 March 2019, according to routine clinical practice and local labeling. Of 123 patients, 78% were women. The mean (standard deviation, SD) age of patients at diagnosis was 40.3 (9.1) years, and the mean time since diagnosis was 13.8 (7.3) years. Patients were previously treated with a median (interquartile range; IQR) number of two (2.0-3.0) disease-modifying treatments (DMTs). Patients were treated with ALZ for a mean (SD) of 29.7 (13.8) months. ALZ reduced the annualized relapse rate (ARR) (1.5 before vs. 0.05 after; p < 0.001) and improved the median EDSS (4.63 before vs. 4.00 after; p < 0.001). Most (90.2%) patients were relapse-free while receiving ALZ. The mean number of gadolinium-enhancing [Gd+] T1 lesions was reduced (1.7 before vs. 0.1 after; p < 0.001), and the mean number of T2 hyperintense lesions was maintained (35.7 before vs. 35.4 after; p = 0.392). A total of 27 (21.9%) patients reported 29 autoimmune diseases: hyperthyroidism (12), hypothyroidism (11), idiopathic thrombocytopenic purpura (ITP) (3), alopecia areata (1), chronic urticaria (1), and vitiligo (1). The mean number of health resources (outpatient visits, emergency room visits, hospital admissions, and tests performed in the hospital) used while patients were treated with ALZ progressively decreased from year 1 to year 4, except for a slight increase at year 2 of outpatient visits. The ReaLMS study provides real-world evidence that ALZ can promote clinical and magnetic resonance imaging disease remission, as well as disability improvement in patients with MS, despite several prior DMT failures. The ALZ safety profile was consistent with data available from clinical trials and other real-world studies. Healthcare resource use was reduced throughout the treatment period.

Ublituximab (Briumvi) for Relapsing Multiple Sclerosis

The FDA has approved the recombinant chimeric anti-CD20 antibody ublituximab-xiiy (Briumvi – TG Therapeutics) for IV treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (initial neurological episode), relapsing-remitting disease, and active secondary progressive MS (SPMS). Two other anti-CD20 antibodies, IV ocrelizumab (Ocrevus) and SC ofatumumab (Kesimpta), are also FDA-approved for these indications.

Are highly active and aggressive multiple sclerosis the same entity?

Are highly active and aggressive multiple sclerosis the same entity?

Early onset of Action and Sustained Efficacy of MRI Outcomes during Cladribine Tablets Treatment in Highly Active Relapsing Multiple Sclerosis: Results of the 2-Year MAGNIFY-MS Study

Early onset of Action and Sustained Efficacy of MRI Outcomes during Cladribine Tablets Treatment in Highly Active Relapsing Multiple Sclerosis: Results of the 2-Year MAGNIFY-MS Study

Improvements in Quality of Life Over 2 Years in Patients Treated with Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: Final Analysis of CLARIFY-MS

Improvements in Quality of Life Over 2 Years in Patients Treated with Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: Final Analysis of CLARIFY-MS

Selective emergence of antibody-secreting cells in the multiple sclerosis brain.

Although distinct brain-homing B cells have been identified in multiple sclerosis (MS), it is unknown how these further evolve to contribute to local pathology. We explored B-cell maturation in the central nervous system (CNS) of MS patients and determined their association with immunoglobulin (Ig) production, T-cell presence, and lesion formation. Exvivo flow cytometry was performed on post-mortem blood, cerebrospinal fluid (CSF), meninges and white matter from 28 MS and 10 control brain donors to characterize B cells and antibody-secreting cells (ASCs). MS brain tissue sections were analysed with immunostainings and microarrays. IgG index and CSF oligoclonal bands were measured with nephelometry, isoelectric focusing, and immunoblotting. Blood-derived B cells were cocultured under T follicular helper-like conditions to evaluate their ASC-differentiating capacity invitro. ASC versus B-cell ratios were increased in post-mortem CNS compartments of MS but not control donors. Local presence of ASCs associated with a mature CD45low phenotype, focal MS lesional activity, lesional Ig gene expression, and CSF IgG levels as well as clonality. Invitro B-cell maturation into ASCs did not differ between MS and control donors. Notably, lesional CD4+ memory T cells positively correlated with ASC presence, reflected by local interplay with T cells. These findings provide evidence that local B cells at least in late-stage MS preferentially mature into ASCs, which are largely responsible for intrathecal and local Ig production. This is especially seen in active MS white matter lesions and likely depends on the interaction with CD4+ memory T cells. Stichting MS Research (19-1057 MS; 20-490f MS), National MS Fonds (OZ2018-003).

Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence

alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9-3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure.

Multiple Sclerosis Is Associated with Immunoglobulin Germline Gene Variation of Transitional B Cells.

The regulatory functions of the B-cell compartment play an important role in the development and suppression of the immune response. Disruption of their anti-inflammatory functions may lead to the acceleration of immunopathological processes, and to autoimmune diseases, in particular. Unfortunately, the exact mechanism underlying the functioning and development of regulatory B cells (Breg) has not yet been fully elucidated. Almost nothing is known about their specificity and the structure of their B-cell receptors (BCRs). In this research, we analyzed the BCR repertoire of the transitional Breg (tBreg) subpopulation with the CD19+CD24highCD38high phenotype in patients with multiple sclerosis (MS), using next-generation sequencing (NGS). We show, for the first time, that the immunoglobulin germline distribution in the tBreg subpopulation is different between MS patients and healthy donors. The registered variation was more significant in patients with a more severe form of the disease, highly active MS (HAMS), compared to those with benign MS (BMS). Our data suggest that during MS development, deviations in the immunoglobulin Breg repertoire occur already at the early stage of B-cell maturation, namely at the stage of tBregs: between immature B cells in the bone marrow and mature peripheral B cells.

Assessment of the efficacy and safety of alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis in Russian population

To evaluate the severity and frequency of infusion reactions (IR) in patients with highly active relapsing-remitting multiple sclerosis (MS) In Russian population receiving alemtuzumab therapy. In retrospective study, we analyzed data from 50 patients with highly active relapsing-remitting multiple sclerosis (MS) from six Regional MS Centers in the Russian Federation who received two courses of alemtuzumab between 2018 and 2022. Among all IRs, the most frequently reported were hives-like rashes, which were registered in 27 people, mostly of mild severity (70.6%). Headaches were the second most common IR, observed in 17 patients (34%). When comparing the group of patients who underwent music therapy (MT) with those who received alemtuzumab therapy without MT, no statistically significant difference was found in the frequency and severity of IRs. All patients experienced IRs of varying degrees of severity. A decrease in the score on the EDSS disability scale was noted. MT did not affect the occurrence or severity of IRs.