Multiple Sclerosis Centers Research Articles

Neuromyelitis optica spectrum disorders with a benign course. Analysis of 544 patients.

Neuromyelitis optica spectrum disorders (NMOSD) most commonly cause severe disability which is related to disease attacks. However, some patients retain good neurological function for a long time after disease onset. To determine the frequency, demographic and the clinical features of good outcome NMOSD, and analyze their predictive factors. We selected patients who met the 2015 International Panel for NMOSD diagnostic criteria from seven MS Centers. Assessed data included age at disease onset, sex, race, number of attacks within the first and three years from onset, annualized relapsing rate (ARR), total number of attacks, aquaporin-IgG serum status, presence of cerebrospinal fluid (CSF)-specific oligoclonal bands (OCB) and the Expanded Disability Status Scale (EDSS) score at the last follow-up visit. NMOSD was classified as non-benign if patients developed sustained EDSS score >3.0 during the disease course, or benign if patients had EDSS score ≤3.0 after ≥15 years from disease onset. Patients with EDSS <3.0 and disease duration shorter than 15 years were not qualified for classification. We compared the demographic and clinical characteristics of benign and non-benign NMOSD. Logistic regression analysis identified predictive factors of outcome. There were 16 patients with benign NMOSD (3% of the entire cohort; 4.2% of those qualified for classification; and 4.1% of those who tested positive for aquaporin 4-IgG), and 362 (67.7%) with non-benign NMOSD, whereas 157 (29.3%) did not qualify for classification. All patients with benign NMOSD were female, 75% were Caucasian, 75% tested positive for AQP4-IgG, and 28.6% had CSF-specific OCB. Regression analysis showed that female sex, pediatric onset, and optic neuritis, area postrema syndrome, and brainstem symptoms at disease onset, as well as fewer relapses in the first year and three years from onset, and CSF-specific OCB were more commonly found in benign NMOSD, but the difference did not reach statistical significance. Conversely, non-Caucasian race (OR: 0.29, 95% CI: 0.07-0.99; p=0.038), myelitis at disease presentation (OR: 0.07, 95% CI: 0.01-0.52; p <0.001), and high ARR (OR: 0.07, 95% CI: 0.01-0.67; p=0.011) were negative risk factors for benign NMOSD. Benign NMOSD is very rare and occurs more frequently in Caucasians, patients with low ARR, and those who do not have myelitis at disease onset.

Multiple Sclerosis in Korea: A Hospital-Based, Multicenter, Epidemiological Study

Background: In the present era of rapidly evolving treatment options, there is a need for better understanding of the epidemiology and current management of patients with multiple sclerosis (MS). A survey was conducted to determine the epidemiologic characteristics and the current treatment status of patients with MS in Korea.Methods: In April 2022, we collected data on patients with MS, including number participating in follow up, sex ratio, current disease modifying treatment (DMT), and disability status (Expanded Disability Status Score, EDSS) from 30 major MS centers in Korea.Results: A total of 1,290 patients with MS was identified, with a female to male ratio of 2.4:1. Geographically, 1,047 patients (81%) were being monitored at hospitals in the capital regions (Seoul, Incheon, and Gyeonggi-do), while 243 (19%) were receiving care at hospitals outside the capital regions. There were 1,199 patients on DMTs, with 876 (73%) taking drugs with moderate efficacy and 264 (22%) taking drugs with high efficacy. Patients with current EDSS score greater than 3.0 and 5.5 numbered 242 (20%) and 105 (9%), respectively.Conclusion: The hospital-based prevalence survey revealed the number and geographical distribution of patients with MS in Korea.

Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial

Multiple sclerosis typically has onset in young adults and new disease activity diminishes with age. Most clinical trials of disease-modifying therapies for multiple sclerosis have not enrolled individuals older than 55 years. Observational studies suggest that risk of return of disease activity after discontinuation of a disease-modifying therapies is greatest in younger patients with recent relapses or MRI activity. We aimed to determine whether risk of disease recurrence in older patients with no recent disease activity who discontinue disease-modifying therapy is increased compared to those who remain on disease-modifying therapy. DISCOMS was a multicentre, randomised, controlled, rater-blinded, phase 4, non-inferiority trial. Individuals with multiple sclerosis of any subtype, 55 years or older, with no relapse within the past 5 years or new MRI lesion in the past 3 years while continuously taking an approved disease-modifying therapy were enrolled at 19 multiple sclerosis centres in the USA. Participants were randomly assigned (1:1 by site) with an interactive response technology system to either continue or discontinue disease-modifying therapy. Relapse assessors and MRI readers were masked to patient assignment; patients and treating investigators were not masked. The primary outcome was percentage of individuals with a new disease event, defined as a multiple sclerosis relapse or a new or expanding T2 brain MRI lesion, over 2 years. We assessed whether discontinuation of disease-modifying therapy was non-inferior to continuation using a non-inferiority, intention-to-treat analysis of all randomly assigned patients, with a predefined non-inferiority margin of 8%. This trial is registered at ClinicalTrials.gov, NCT03073603, and is completed. 259 participants were enrolled between May 22, 2017, and Feb 3, 2020; 128 (49%) were assigned to the continue group and 131 (51%) to the discontinue group. Five participants were lost to follow-up (continue n=1, discontinue n=4). Six (4·7%) of 128 participants in the continue group and 16 (12·2%) of 131 in the discontinue group had a relapse or a new or expanding brain MRI lesion within 2 years. The difference in event rates was 7·5 percentage points (95% CI 0·6-15·0). Similar numbers of participants had adverse events (109 [85%] of 128 vs 104 [79%] of 131) and serious adverse events (20 [16%] vs 18 [14%]), but more adverse events (422 vs 347) and serious adverse events (40 vs 30) occurred in the discontinue group. The most common adverse events were upper respiratory infections (20 events in 19 [15%] participants in the continue group and 37 events in 30 [23%] participants in the discontinue group). Three participants in the continue group and four in the discontinue group had treatment-related adverse events, of which one in each group was a serious adverse event (multiple sclerosis relapse requiring admission to hospital). One participant in the continue group and two in the discontinue group died; no deaths were deemed to be related to treatment. We were unable to reject the null hypothesis and could not conclude whether disease-modifying therapy discontinuation is non-inferior to continuation in patients older than 55 years with multiple sclerosis and no recent relapse or new MRI activity. Discontinuation of disease-modifying therapy might be a reasonable option in patients older than 55 years who have stable multiple sclerosis, but might be associated with a small increased risk of new MRI activity. Patient-Centered Outcomes Research Institute and the National Multiple Sclerosis Society.

Cerebrospinal Fluid Chloride Is Associated with Disease Activity of Relapsing-Remitting Multiple Sclerosis: A Retrospective Cohort Study.

Blood-brain barrier dysfunction in active multiple sclerosis (MS) lesions leads to pathological changes in the cerebrospinal fluid (CSF). This study aimed to investigate the possible association between routine CSF findings, especially CSF chloride, at the time of the first lumbar puncture and the relapse risk and disability progression of relapsing-remitting MS (RRMS). This retrospective study included 77 patients with RRMS at the MS Center of our institution from January 2012 to December 2020. The Anderson and Gill (AG) model and Spearman correlation analysis were used to explore predictors of relapse and disability during follow-up. In the multivariate AG model, patients with elevated CSF chloride level (hazard ratio [HR], 1.1; 95% confidence interval [CI]: 1.06-1.22; p = 0.001) had a high risk of MS relapse. Using median values of CSF chloride (123.2 mmol/L) as a cut-off, patients with CSF chloride level ≥ 123.2 mmol/L had a 120% increased relapse risk compared with those with CSF chloride level < 123.2 mmol/L (HR = 2.20; 95% CI: 1.19-4.05; p = 0.012). Elevated CSF chloride levels might be a biologically unfavorable predictive factor for disease relapse in RRMS.

Late-Breaking Abstracts from the 2023 Annual Meeting of the Consortium of Multiple Sclerosis Centers: May 31-June 3, 2023 • Aurora, Colorado

Late-Breaking Abstracts from the 2023 Annual Meeting of the Consortium of Multiple Sclerosis Centers: May 31-June 3, 2023 • Aurora, Colorado

High serum neurofilament levels are observed close to disease activity events in pediatric-onset MS and MOG antibody-associated diseases.

Serum neurofilament light chain (sNfL) is an emerging multiple sclerosis (MS) biomarker which measures neuro-axonal damage. However, understanding its temporal association with disease activity in pediatric-onset MS (POMS) and Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains limited. To investigate the association of sNfL levels and time from disease activity in children with MS and MOGAD. POMS and MOGAD cases with onset before 18 years of age were enrolled at the University of California San Francisco (UCSF) Regional Pediatric MS Center. Frequency-matched healthy subjects were recruited from general pediatric clinics. Serum samples were tested for MOG-IgG at Mayo Clinic using a live cell-based fluorescent activated cell sorting assay. sNfL levels were measured using single-molecule array (Simoa) technology measured in pg/mL. Data on demographics, clinical features, MRI, CSF, and treatment data were collected by chart review. We included 201 healthy controls healthy controls, 142 POMS, and 20 confirmed MOGAD cases with available sNfL levels. The median (IQR) age at the time of sampling was 15.6 (3.9), 15.5 (3.1), and 8.8 (4.1) years for controls, POMS, and MOGAD, respectively. Median sNfL levels (pg/ml) were higher in POMS (19.6) and MOGAD (32.7) cases compared to healthy controls (3.9) (p<0.001). sNfL levels ≥100 pg/ml were only detected within four months of a clinical event or MRI activity in both POMS and MOGAD cases. In addition, sNfL levels were higher in POMS patients with new/enlarged T2 and gadolinium-enhanced lesions than those without MRI activity within four months of sampling in POMS cases. High sNfL levels were observed close to clinical or MRI events in POMS and MOGAD. Our findings support sNfL as a biomarker of disease activity in pediatric demyelinating disorders.

Discontinuation of first-line disease-modifying therapy in relapse onset multiple sclerosis.

It is not known if and when first-line disease modifying therapy (DMT) can safely be discontinued in relapse onset multiple sclerosis (MS) patients. To investigate the characteristics of patients who discontinued first-line DMT, and the occurrence of clinical and radiological inflammatory disease activity after discontinuation. We collected clinical and MRI parameters from patients with relapse onset MS in the MS Center Amsterdam and Rijnstate Hospital Arnhem who discontinued first-line DMT with no intention of restarting or switching treatment. In total, 130 patients were included in the analyses. After discontinuation, 78 patients (60%) experienced disease activity. Sixty-three patients (48.5%) showed MRI activity after DMT discontinuation, 40 patients (30.8%) experienced relapse(s), and 29 patients (22.3%) restarted DMT. Higher age at DMT discontinuation was associated with a lower risk of MRI activity (45 -55vs. <45 years: OR 0.301, p=0.007, >55vs. <45 years, OR: 0.296, p=0.044), and with a lower risk of relapse(s) after discontinuation (45-55vs. <45 years: OR=0.495, p=0.106, >55vs. <45 years: OR=0.081, p=0.020). Higher age at first-line DMT discontinuation is associated with lower risk and severity of radiological disease activity in MS, and a lower risk of relapse(s) after discontinuation.

12‐weeks of caloric restriction diet improves cortical cerebral blood flow in healthy middle‐age adults

AbstractBackgroundCaloric restriction (CR) improves neuronal stress resistance in animals and improves cognitive performance in older adults (1‐3). Neuroinflammation is an increasingly recognized mechanism relevant to Alzheimer disease (AD). We investigated the effect of a 12‐week CR diet on imaging markers of dementia and neuroinflammation in midlife individuals with multiple sclerosis (MS), a prototype neuroinflammatory disease.MethodsIn a single‐blind randomized controlled trial, 10 participants with MS (8 women and 2 men, age: 45.5±10.67 and education: 16.4±2.5 years) were recruited from the Washington University John L. Trotter MS Center and randomly assigned to participate in either a 12‐week CR or control group on their regular diet. Participants fasted 2 days a week and during those days eating no more than 500 calories. Participants underwent MRI scanning at the time of recruitment and at the end of the 12‐week program. Volumetric analyses were conducted through FreeSurfer 7.1.1 (4), relative regional cerebral blood flow (rCBF) was obtained through ASL‐MRICloud (5), and hindered and restricted diffusion fractions (HF and RF) were calculated through the diffusion basis spectrum imaging (DBSI), representing tissue edema and inflammatory cell infiltration respectivelyResultsSix participants were obese, two were overweight and two had normal weight with an average BMI of 30.3±5.48 kg/m2 across participants. Following 12‐weeks of CR, participants showed an increase in normalized hippocampal volume (p:0.02) compared to those on regular diet. CR also resulted in improved cortical thickness in the bilateral medial orbitofrontal cortices compared to the control group (p:0.014). An average increase in relative perfusion (rCBF) in the bilateral inferior temporal gyri (p:0.02, &amp; p:0.004) and bilateral fusiform gyri (p:0.008 &amp; p:0.002) was observed in participants undergoing CR compared to those on a regular diet at the end of 12‐weeks (Figure 1 and 2). Being on a CR diet was associated with reduced HF and RF in the bilateral inferior longitudinal fasciculi (p:0.04 &amp; p:0.002) indicating reduced edema and cellularity (6).ConclusionCR is associated with alterations in brain’s structure and function in terms of improved volumetric measurements, regional perfusion and reduced tissue inflammation, and hence implicated as a neuroprotective intervention in midlife persons.

The consequences of switching from Gilenya® to generics for fingolimod.

On May 2017, two generic drugs for fingolimod were introduced into the market in Israel, and most MS patients treated with Gilenya® (Novartis) were switched to fingolimod (Teva), or to Finolim (Rafa). In this study we analyzed the consequences of switching to generic fingolimod in a single MS center. Study population included relapsing MS patients who were treated with Gilenya® for at least two year before May 2017, switched to generic fingolimod and remained on treatment for at least 2 years thereafter. Data before and after the switch were compared. Twenty-seven patients fulfilled the inclusion criteria (F=20, RRMS=20, SPMS=7, average age 49±11.4 years, average disease duration=16.6±7.6 years). Seventeen patients had to be switched back to the original Gilenya® due to intolerable new or worsening clinical adverse events (n=9), clinical relapse (n=1), clinical relapse with adverse events (n=3), elevation of liver enzymes > X3 ULN (n=3) and elevation of amylase (n=1). Expanded Disability Status Scale (EDSS) score increased in 4 patients during the year before the switch, and in 12 patients during the year of treatment with generic fingolimod (p=0.036). The tolerability, retention rate and probably efficacy of generic fingolimod seems to be lower than the original Gilenya®.

Implementing physical activity vital sign as a self-reported measure of physical activity in patients with multiple sclerosis in a clinical setting.

Routinely assessing exercise levels during clinical visits may be a starting point for clinicians to support physical activity inpersons with multiple sclerosis (MS). To evaluate the feasibility and findings of routinely implementing a self-reported physical activity vital sign during clinical visits. Retrospective database review. Outpatient academic MS center. All adult patients of our MS center with confirmed MS presenting for an in-person or telemedicine clinic visit with a physician or nurse practitioner. None. A standard physical activity vital sign representing minutes per week of moderate-to-vigorous exercise was collected. Percentage of persons with MS with a recorded physical activity vital sign was retrospectively evaluated along with demographic characteristics and key findings. Ninety-three percent of patients with MS at our center had a physical activity vital sign recorded in at least one visit, and 86% at the most recent visit. Of 1560 patients with a recorded physical activity vital sign, 24.3% of patients were consistently active (≥150 min/week of exercise), 20.8% were consistently inactive (0 min/week), and the remaining 54.9% were inconsistently active. The physical activity vital sign was inversely associated with BMI (p < .001) and 25-foot walk test times (p < .001), but not associated with biological sex or age. Approximately a quarter of patients with MS with a documented physical activity vital sign met national aerobic exercise guidelines of 150 min/week per the U.S. Department of Health and Human Services. Routine implementation of the physical activity vital sign at our MS center was feasible and helped identify inactive patients who may benefit from physical activity counseling.

Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis

Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. AHSCT vs fingolimod, natalizumab, or ocrelizumab. Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.

Tailoring Rituximab According to CD27-Positive B-Cell versus CD19-Positive B-Cell Monitoring in Neuromyelitis Optica Spectrum Disorder and MOG-Associated Disease: Results from a Single-Center Study.

B-cell-depleting agents have been widely used for neuromyelitis optica spectrum disorder (NMOSD) and MOG-associated diseases (MOGAD), but no consensus exists on the optimal dose and frequency of treatment administration. The aim of our study was to evaluate the effect of a Rituximab (RTX) personalized treatment approach based on CD27-positive B-cell monitoring on efficacy, safety, and infusion rates. This is a retrospective, uncontrolled, single-center study including patients with NMOSD and MOGAD treated with RTX at a tertiary multiple sclerosis center at the San Luigi University Hospital, Orbassano, Italy. All the patients were treated with RTX induction, followed by maintenance infusion at the dosage of 1000mg according to cell repopulation: initially according to total CD19-positive B-cell monitoring (>0.1% of lymphocytes), and subsequently according to CD27-positive B-cell repopulation (>0.05% of lymphocytes for the first 2years, and subsequently>0.1%). NMOSD and MOGAD activity was assessed as clinical or MRI activity. All patients were screened of the occurrence of severe adverse events (AEs). A total of 19 patients were included in the analysis. Median follow-up was 7.64years (range 3.09-16.25). The annualized relapse rate (ARR) 1year before RTX start was 2.37 [Standard deviation (SD), 1.34] and decreased to 0.08 (SD 0.11) in the subsequent years after RTX initiation. ARR did not differ before and after start of CD27 monitoring. Median inter-dose time was 8.80 (range 5.78-14.23) before CD27 monitoring and 15.93months (range 8.56-35.37) after CD27 monitoring (p<0.001). We observed no AEs. Our findings suggest that in our cohort CD27-positive B-cell-based RTX reinfusion regimen was able to reduce the number of RTX reinfusions relative to CD19-positive B-cell monitoring, with comparable efficacy and safety profile. In order to achieve an even more individualized and effective treatment, the FCGR3A genetic polymorphisms could be evaluated when assessing RTX efficacy.

Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs

Background: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax. Objectives: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ). Methods: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use. Results: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed. Conclusion: Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.

Abstracts from the 37th Annual Meeting of the Consortium of Multiple Sclerosis Centers: May 31-June 3, 2023 · Aurora, Colorado

Abstracts from the 37th Annual Meeting of the Consortium of Multiple Sclerosis Centers: May 31-June 3, 2023 · Aurora, Colorado

Longitudinal Olfactory Patterns in Multiple Sclerosis: A Scoping Review and Implication for Use in Management of Disease.

Although studies regarding multiple sclerosis (MS) and olfactory dysfunction (OD) have been previously described and summarized, there is not a sole review of longitudinal studies regarding the matter. This review examines the existing literature investigating MS and its effect on olfaction. In addition, the role of OD in the diagnosis and prognosis of MS is explored. A scoping review of the literature was performed covering longitudinal studies investigating MS and OD. Systematic searches of PubMed, Google Scholar, Web of Science, Embase, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, AgeLine, and MEDLINE were performed using terms that encompassed MS and olfaction. The aim of this review was to build on the existing literature by summarizing only findings that were demonstrated longitudinally. Of 6938 articles identified from the search, 9 met the inclusion criteria: longitudinal observation of relapsing-remitting or progressive MS. Olfaction was measured and scored using various testing arrays, and these scores were then correlated with a multitude of clinical markers. Across all studies, patients with MS demonstrated increased OD. Longitudinally, 2 contrasting patterns were identified: (1) clinical markers of acute inflammation correlated with an increased odor threshold and (2) clinical markers of neurodegeneration, or progression of disease, correlated with a decreased ability to discriminate and identify odors. These studies suggest that olfaction is a dynamic, dependent variable of neurodegeneration, correlating with inflammation and clinical markers. This opens the door for future exploration of olfaction's relationship with MS diagnosis, characterization, and therapeutic response.

The Czech National MS Registry (ReMuS): Data trends in multiple sclerosis patients whose first disease-modifying therapies were initiated from 2013 to 2021.

Multiple sclerosis treatment strategies are changing in the Czech Republic. According to data from 2013-2021, the proportion of patients starting high-efficacy disease-modifying therapies is increasing. In this survey, we describe the actual data trends in multiple sclerosis (MS) patients beginning their first disease‑modifying therapies (DMTs) from 2013 to 2021. The secondary objective was to present the history, data collection, and scientific potential of the Czech National MS registry (ReMuS). First, using descriptive statistics, we analysed the data for patients starting their first DMTs, either platform (including dimethyl fumarate) or high-efficacy DMTs (HE-DMTs), for each successive year. Second, a detailed description of the history, data collection, completeness, quality optimising procedures, and legal policies of ReMuS is provided. Based on the dataset from December 31, 2021, the total number of monitored patients with MS in ReMuS increased from 9,019 in 2013 (referred from 7 of 15 MS centres) to 12,940 in 2016 (referred from all 15 Czech MS centres) to 17,478 in 2021. In these years, the percentage of patients treated with DMTs in the registry ranged from 76 to 83%, but the proportion of patients treated with HE-DMTs changed from 16.2% in 2013 to 37.1% in 2021. During the follow-up period, a total of 8,491 treatment-naive patients received DMTs. The proportion of patients (all MS phenotypes) starting HE-DMTs increased from 2.1% in 2013 to 18.5% in 2021. Patient registries, including ReMuS, provide an essential quality data source, especially in light of the increasing percentage of patients on HE-DMTs. Although early initiation of HE-DMT can provide considerable benefits, it also carries greater potential risks. Consistent long-term follow-up of patients in real‑world clinical practice, which only registries allow, is therefore crucial to evaluate the efficacy and safety of therapeutic strategies, for epidemiological research and to assist decision making by healthcare providers and regulatory bodies.

Demographic Features and Clinical Course of Patients With Pediatric-Onset Multiple Sclerosis on Newer Disease-Modifying Treatments

BackgroundTreatment of pediatric-onset multiple sclerosis (POMS) is challenging given the lack of safety and efficacy data in the pediatric population for many of the disease-modifying treatments (DMTs) approved for use in adults with MS. Our objective was to describe the demographic features and clinical and radiologic course of patients with POMS treated with the commonly used newer DMTs within the US Network of Pediatric MS Centers (NPMSC). MethodsThis is an analysis of prospectively collected data from patients who initiated treatment before age 18 with the DMTs listed below at the 12 regional pediatric MS referral centers participating in the NPMSC. ResultsOne hundred sixty-eight patients on dimethyl fumarate, 96 on fingolimod, 151 on natalizumab, 166 on rituximab, and 37 on ocrelizumab met criteria for analysis. Mean age at DMT initiation ranged from 15.2 to 16.5 years. Disease duration at the time of initiation of index DMT ranged from 1.1 to 1.6 years with treatment duration of 0.9-2.0 years. Mean annualized relapse rate (ARR) in the year prior to initiating index DMT ranged from 0.4 to 1.0. Mean ARR while on index DMT ranged from 0.05 to 0.20. New T2 and enhancing lesions occurred in 75%-88% and 55%-73% of the patients, respectively, during the year prior to initiating index DMT. After initiating index DMT, new T2 and enhancing lesions occurred in 0%-46% and 11%-34% patients, respectively. Rates of NEDA-2 (no evidence of disease activity) ranged from 76% to 91% at 6 months of treatment with index DMTs and 66% to 84% at 12 months of treatment with index DMTs. ConclusionsThough limited by relatively short treatment duration with the index DMTs, our data suggest clinical and MRI benefit, as well as high rates of NEDA-2, in a large number of POMS patients, which can be used to guide future studies in this population.

Discordant Race and Ethnicity Documentation in the Georgetown Multiple Sclerosis and Neuroimmunology Center (P4-9.005)

<h3>Objective:</h3> We aimed to evaluate the reliability of R/E documentation in the EHR of MedStar Georgetown University Hospital. <h3>Background:</h3> The incidence and prevalence of multiple sclerosis (MS) appears to vary by race and ethnicity (R/E), and prognosis has been reported to be worse in Black and Hispanic/Latinx MS patients compared to White MS patients. Frequently, studies rely on electronic health records (EHR), but discrepancies in R/E documentation may be a potential source of errors in health disparities assessment. <h3>Design/Methods:</h3> Self-reported data from the MS-ADVANCE study at Georgetown University was compared to demographics extracted from the MedStar Georgetown University Hospital EHR. Concordance was defined as the percent agreement between self-reported R/E and R/E demographic information found in the EHR. <h3>Results:</h3> R/E data from 197 participants in the MS-ADVANCE study were analyzed. Most participants self-reported as Non-Hispanic White (n=142), which generally matched EHR documentation (concordance 92.6%). Similarly, 86% of Non-Hispanic Black (n=43) and 100% of Asian individuals (n=2) were accurately identified in the EHR. However, only 2 of 8 self-identified Hispanic/Latinx patients were identified as such in the EHR (concordance 25%). <h3>Conclusions:</h3> This is the first study evaluating concordance of self-reported R/E information compared to EHR documentation in patients with MS. While concordance was generally good in most groups, R/E information in the EHR was often incorrect for Hispanic/Latinx patients. Because most epidemiological analyses extract data from electronic records, this considerable observed discrepancy in R/E documentation may impact our understanding of prevalence, incidence, and prognosis in Hispanic/Latinx individuals with MS. Since obtaining reliable demographic information is crucial to determine quality of care and health outcomes, improvement in data collection is necessary when exploring healthcare disparities in Hispanic/Latinx individuals living with MS. <b>Disclosure:</b> Dr. Manrique has nothing to disclose. Miss Peres Da Silva has nothing to disclose. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myer Squibb. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Peter Angelos Law Firm. Dr. Osborne has received publishing royalties from a publication relating to health care. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sanofi Genzyme. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Biogen. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Celgene. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Shin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Celgene. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Shin has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Mallinckrodt.

Efficacy of tixagevimab/cilgavimab as pre-exposure prophylaxis to prevent symptomatic COVID-19 infection in Multiple Sclerosis and Related Disorders: a real-world observational study (S31.010)

<h3>Objective:</h3> To evaluate the risk of breakthrough symptomatic Coronavirus Disease 2019 (COVID-19) infections after tixagevimab/cilgavimab administration for pre-exposure prophylaxis in multiple sclerosis and related disorders (MSRD) patients on immunosuppressive therapy in real-world practice. <h3>Background:</h3> The use of a monoclonal-antibody combination tixagevimab/cilgavimab has been shown to be effective for pre-exposure prophylaxis in patients with risk factors for severe symptomatic COVID-19 infection. However, tixagevimab/cilgavimab effectiveness in MSRD patients on immunosuppressive therapy has not been comprehensively investigated. <h3>Design/Methods:</h3> Retrospective review of MSRD patients evaluated at the Cedars-Sinai Multiple Sclerosis and Neuroimmunology center between January 1, 2022, to October 10, 2022. Patient clinical characteristics, comorbidities, disease modifying therapy, COVID-19 vaccination status, tixagevimab/cilgavimab administration status, and symptomatic COVID-19 infection occurrence were evaluated. Propensity score matching using multivariable logistic regression was used to analyze the effect of tixagevimab/cilgavimab on breakthrough COVID-19 infection accounting for age, sex, race, disease modifying therapy, and COVID-19 vaccination. <h3>Results:</h3> A total of 348 MSRD patients were included in the analysis, among which 64 (18%) received tixagevimab/cilgavimab, and 284 (82%) did not (mean age 50±13 and 52±13 years, 80% and 69% female, respectively). Most common indications for tixagevimab/cilgavimab were anti-CD20 therapy (83%) and sphingosine-1-phosphate receptor modulator therapy (5%). Using propensity score matching, the probability of observing symptomatic COVID-19 infection in the tixagevimab/cilgavimab group was lower by 11.0% (p=0.01; 95% CI 3–19%). Breakthrough infections on tixagevimab/cilgavimab occurred in 4 cases (8%), 3 of which occurred in patients receiving medications suppressing B and T lymphocyte proliferation (two cases on mycophenolate mofetil, and one case with prior history of cyclophosphamide and mitoxantrone treatment). <h3>Conclusions:</h3> In this retrospective observational study, tixagevimab/cilgavimab injection was associated with a lower incidence of symptomatic COVID-19 infection in MSRD patients on immunosuppressive therapy. Breakthrough COVID-19 infections on tixagevimab/cilgavimab were observed in patients with current or prior exposure to medications suppressing B and T lymphocyte proliferation. <b>Disclosure:</b> Dr. Tan has nothing to disclose. Ms. Locke has nothing to disclose. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care. Dr. Guerrero has nothing to disclose. The institution of Dr. Sicotte has received research support from Biogen. The institution of Dr. Sicotte has received research support from PCORI. The institution of Dr. Sicotte has received research support from NIH. The institution of Dr. Sicotte has received research support from NMSS. Dr. Sicotte has a non-compensated relationship as a National Medical Advisory Committee Chair with National MS Society that is relevant to AAN interests or activities. The institution of Dr. Al-Louzi has received research support from the National Multiple Sclerosis Society and American Brain Foundation.

Efficacy of Early Ofatumumab vs Late Switch From Teriflunomide: Subgroup Analysis of the ALITHIOS Open-label Extension Study by Previous Disease-Modifying Therapy Exposure and Age (P6-3.016)

Efficacy of Early Ofatumumab vs Late Switch From Teriflunomide: Subgroup Analysis of the ALITHIOS Open-label Extension Study by Previous Disease-Modifying Therapy Exposure and Age (P6-3.016)