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Background: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). Methods: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. Results: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. Conclusions: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration.

Made available in DSpace on 2022-04-28T19:46:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-09 Background and ObjectivesPeople with multiple sclerosis MS are a vulnerable group for severe coronavirus disease 2019 COVID-19, particularly those taking immunosuppressive disease-modifying therapies DMTs. We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data sources in 28 countries were aggregated sources could include patients from 1-12 countries. Demographic age, sex, clinical MS phenotype, disability, and DMT untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit ICU admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale EDSS score.ResultsSix hundred fifty-seven 28.1% with suspected and 1,683 61.9% with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02 and ICU admission aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89, although only rituximab was associated with higher risk of artificial ventilation aOR 4.00, 95% CI 1.54-10.39. Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07 and ICU admission aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23, but only rituximab was associated with artificial ventilation aOR 6.15, 95% CI 3.09-12.27. Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92 and ICU admission aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91, but only rituximab was associated with ventilation aOR 5.52, 95% CI 1.71-17.84. Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.DiscussionUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19. CORe Department of Medicine and Neuroepidemiology Unit Melbourne School of Population and Global Health Menzies Institute for Medical Research University of Tasmania ESAT-STADIUS KU Leuven Department of Neurology Melbourne MS Centre Royal Melbourne Hospital MS International Federation Department of Clinical Neuroscience Swedish MS Registry Department of Neurology CHU Pontchaillou Karolinska Institutet Biomedical Research Institute-Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Department of Computer Science and AI KU Leuven QMENTA Medpace Reference Laboratories Molecular Unit IConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData German MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbH MS Register Swansea University COViMS Division of Biostatistics Washington University in St. Louis Mellen Center for Multiple Sclerosis Cleveland Clinic Department of Neuroscience Central Clinical School Monash University Al-Amiri Hospital Kuwait City Dokuz Eylul University Neurology Department Hospital Universitario de CEMIC RELACOEM Australian MS Longitudinal Study Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista Unesp Faculdade de Medicina REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Multiple Sclerosis University Center Ramos Mejia Hospital-EMA Imperial College Swansea University Mental Health Area MS and Demyelinating Diseases Hospital Británico de Buenos Aires EMA Servei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Cemcat Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Institute of Experimental Neurology Ospedale San Raffaele Universidade Estadual Paulista Unesp Faculdade de Medicina

Background: Many individuals with multiple sclerosis (MS) depart the workforce prematurely. In the United States, access to insurance, including health, disability income, long-term care, and life insurance, is largely employment-based or purchased from earnings. Many individuals we see in the clinic experience financial hardship because of a lack of insurance, even if working. We sought to determine the proportion of workers who are financially protected through insurance coverage and the sources of this coverage in a large sample. Methods: We developed an online survey and opened it to individuals aged 18 to 65 years registered with the North American Research Committee on Multiple Sclerosis, iConquerMS, or the National Multiple Sclerosis Society Minority Advisory Council. Data collected included demographic and disease characteristics, current information about each insurance type (coverage vs no coverage), and when the current insurance policies were obtained relative to MS diagnosis. Results: Of 2507 survey respondents, 82.9% were female, 3.8% Hispanic/Latino, and 91.2% White. The mean ± SD age was 53.5 ± 8.5 years and disease duration was 16.4 ± 8.5 years after diagnosis. The most frequently held insurance types were health (96.3%) and life (58.8%). Only 9.7% of respondents had long-term care insurance. Except for life insurance, most current policies were obtained after MS diagnosis. Conclusions: Individuals with MS might not prioritize the possible short- and long-term benefits of these types of insurance. Health care providers can direct patients to nonprofit agencies that educate about of these insurance types and emphasize that others with MS have obtained these insurance types after their diagnosis.

Interferon-β, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS.Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs.In comparison to other DMTs, we did not find evidence of protective effects of interferon-β on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-β. This study does not support the use of interferon-β as a treatment to reduce COVID-19 severity in MS.

Background: For unclear reasons, minorities have been historically underrepresented in multiple sclerosis (MS) clinical trials. We hypothesized that different perceptions and preferences about research participation among racial and ethnic groups contribute to this imbalance. Methods: Members of the MS Minority Research Engagement Partnership Network developed a Web-based survey in English and Spanish on research impressions, concerns, and preferences regarding study attributes among people with MS. Invitations to take the survey were distributed by network members and partner organizations. Results: We included 2599 participants with MS (2111 White, 215 African American; 188 Hispanic). Consistently disliked study attributes included potential harms to health and confusing study information. Compared with White and non-Hispanic participants, respectively, African American (odds ratio [OR] = 2.05, P ≤ .001) and Hispanic (OR = 1.79, P = .003) participants were more concerned about being used by the research team. Hispanic participants were more concerned about research participation carrying risks to their legal status (OR = 1.70, P = .001). Hispanic (OR = 3.18, P ≤ .001) and African American (OR = 5.51, P ≤ .001) participants were more likely to prefer for the study to benefit their own racial/ethnic group. A top concern across all groups was not being fully informed about the research. Conclusions: We found strong support for research across racial and ethnic groups; however, minority groups have specific concerns regarding mistrust, receiving poor-quality care, unemployment, health insurance, and legal status. Investigators wanting to recruit a diverse study population are advised to show how they have addressed these concerns and to communicate how the research will advance the science and literature and result in better care and/or other benefits to underrepresented communities.

Background Patient-reported outcomes (PROs) are widely measured in multiple sclerosis (MS) studies. However, the quality of instrument development processes varies, raising concerns about the meaningfulness of associated data. Objectives To review the development of selected PROs commonly used in MS studies, including definitions of the concepts measured, use of conceptual frameworks, and degree of input from people living with MS (PlwMS). To gain insights and recommendations from PlwMS on their experience with these PROs. Methods We assessed 6 PROs (FSIQ-RMS, modified-FIS, MSQoL-54, Leeds 8-item MSQoL, MSIS-29 and EQ-5D) for alignment with regulatory and scientific requirements on PRO structure/development. PlwMS evaluated the degree to which the PROs reflect disease aspects they perceive important. Results Definitions, clarifications and conceptualisations of the measurement variables were often lacking. PlwMS were variably involved in PRO development. Ethnic diversity was rarely documented. PlwMS identified individualisation, ease of understanding, time burden, and mode of administration as factors affecting PRO usability. Conclusions To date, the PRO development process has consistently lacked clear definitions of concepts of interest, use of conceptual frameworks and patient involvement, thereby compromising the validity of data they generate. PRO instrument development must be conducted more robustly to maximise the value of pivotal clinical trials.

Background and Objectives Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed.Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab.Results Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1–7] and 7% [95% CI 4–11]), ICU/artificial ventilation (2% [95% CI 0–4] and 4% [95% CI 2–6]), and death (1% [95% CI 0–2] and 2% [95% CI 1–4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2–8), 3% (95% CI 1–5), and 1% (95% CI 0–3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19.Discussion Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19. BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.

Multiple sclerosis (MS), a neuroinflammatory disorder, occurs as non-progressive or progressive phenotypes, both forms present with diverse symptoms that may reduce quality of life (QoL). Adherence to healthy lifestyle behaviors has been associated with higher QoL in people with MS, whether these associations differ based on MS phenotype is unknown. Cross-sectional self-reported observational data from 1108 iConquerMS participants were analysed. Associations between lifestyle behaviors and QoL were assessed by linear regression, and phenotype differences via moderation analyses. Diet, wellness, and physical activity, but not vitamin D or omega-3 supplement use, were associated with QoL. Specifically, certain diet types were negatively associated with QoL in relapsing-remitting MS (RRMS), and positively associated in progressive MS (ProgMS). Participation in wellness activities had mixed associations with QoL in RRMS but was not associated in ProgMS. Physical activity was positively associated with QoL in RRMS and ProgMS. Phenotype differences were observed in diet and wellness with physical QoL, and physical activity with most QoL subdomains. Our findings show lifestyle behaviors are associated with QoL and appear to differ based on MS phenotype. Future studies assessing timing, duration, and adherence of adopting lifestyle behaviors may better inform their role in MS management.

Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS). Clinical and real-world studies of DRF have demonstrated improved gastrointestinal (GI) tolerability and low ( 1%) GI-related treatment discontinuation versus dimethyl fumarate (DMF) and high rates of treatment adherence. Our aim was to conduct a concept elicitation study to identify treatment-related concepts most meaningful to patients and to evaluate how these concepts shape the patient perspective of DRF.In-depth qualitative interviews were conducted with patients from October to December 2020. US adults who had been prescribed DRF through routine clinical care and had taken DRF for ≥ 3 weeks in the past 6 months were eligible to participate. Semi-structured interviews explored patient perceptions on treatment selection and impact.Seventeen patients participated in the study. Mean (SD) age was 49.3 (12.0) years. Sixteen patients reported prior disease-modifying therapy, while 10 (58.8%) had prior DMF. DRF treatment duration ranged from ~ 6 weeks to 10 months. Four key concepts emerged: (1) overall wellness and quality of life, (2) ease of administration, (3) minimal and manageable side effects, and (4) patient optimism due to MS treatments. Mode of administration (82.4%), no/mild side effects (70.6%), convenience over injectable/infusion medications (58.8%), and effectiveness (64.7%) were cited as positive aspects of DRF treatment. Frequent dosing (52.9%) and food requirements (41.2%) were cited as negative attributes; however, 94.1% had no dietary changes since starting treatment.The patient perspective is a key aspect when considering a disease-modifying therapy for MS, given the multitude of options currently available. Overall wellness, ease of administration, and minimal and manageable side effects were DRF-related concepts most meaningful to patients on therapy. Acknowledging these patient perceptions in shared decision-making may lead to greater patient adherence and optimal treatment outcomes.Multiple sclerosis (MS), an immune-related disease, may present with neurological symptoms that come and go. Diroximel fumarate (DRF) is a next-generation oral treatment for MS, which has been shown in clinical trials to have fewer gastrointestinal side effects compared to dimethyl fumarate (DMF), another oral treatment. Patients’ perspective can shed light on what they value when choosing a treatment, so we interviewed 17 people with MS about how DRF treatment affects their daily life and work. The study participants (49.3 years old on average) received DRF for ~ 6 weeks to 10 months. Around 5 in 10 people had positive feelings about their current health following treatment with DRF. Most felt there was either improvement or no negative change in quality of life since starting DRF treatment; DRF did not affect their work or daily obligations. Treatment characteristics of DRF that were perceived as most important included ease of administration, minimal and manageable side effects, and the facilitation of overall wellness and quality of life. While the oral dosing of DRF was more convenient than injectable or infusion therapy options, about half of the respondents preferred a less frequent treatment regimen than the twice daily dosing of DRF which needs to be taken with food. However, those who switched to DRF from DMF (or other oral medications for MS) expressed that the transition was smooth. Understanding factors that are important to patients can guide treatment choices and help patients stay on treatment longer and have better MS outcomes.

Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer-acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other) covariates were queried, alongside COVID-19 hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS phenotype, and EDSS. Results 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed/confirmed-only COVID-19, 20.9%/26.9% were hospitalised, 5.4%/7.2% were admitted to ICU, 4.1%/5.4% required artificial ventilation, and 3.2%/3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions Despite the cross-sectional design of this study, the internal and external consistency of these results with prior studies suggests their use may be a risk factor for more severe COVID-19. Key messages Anti-CD20 DMTs may be associated with worse COVID-19 severity amongst people with multiple sclerosis.

Background Multiple sclerosis (MS) comprises progressive and non-progressive phenotypes, both presenting with symptoms that may reduce quality of life (QoL). Lifestyle behaviours, including diet, exercise, and wellness activities, are associated with higher QoL, however little is known about differences by MS phenotype. We assessed associations between lifestyle behaviours and QoL, between progressive vs non-progressive MS. Methods Self-reported cross-sectional data from the iConquerMS study (n = 1,109) were analysed. Lifestyle behaviours were queried via tick-box options for diet-type, supplement use, and wellness activities; and physical activity via Godin-Shephard Leisure-Time Physical Activity Questionnaire. QoL was queried via Neuro-QoL. Linear regression, adjusted for age, sex, BMI, education, disability, and MS duration, was used to assess associations and moderation analyses to assess differences between MS phenotypes. Results Diet-type, physical activity, and wellness activities were associated with specific QoL subdomains. Only associations between diet and physical activity, with QoL subdomains, differed between phenotypes. Anti-inflammatory diets were associated with a 1.5-point increase in mobility in progressive MS. In non-progressive MS, high physical activity was associated with a 3.6-point decrease in depression, and a 4.2-, 2.3- and 3.0-point increase in positive affect, fine motor skills, and social participation, respectively. Conclusions Specific lifestyle behaviours were associated with QoL subdomains. Associations between diet and physical activity with QoL differed between MS phenotype. Key messages Specific lifestyle behaviours are associated with higher QoL. Lifestyle interventions for MS management should consider disease course.

Background and ObjectivesThere are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis–specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS.MethodsBetween 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity.ResultsIn 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction.DiscussionSARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.

BackgroundPeople with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression.Results657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.ConclusionsUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

Highlights • 1,019 people with MS (PwMS) were surveyed online during the COVID-19 pandemic in April 2020. • A majority reported interruptions to MS care and limited access to COVID-19 testing. • Worry about COVID-19 was higher in female and non-white PwMS. • 10% of PwMS reported changing their disease modifying therapy in some way as a result of COVID-19., Background People with multiple sclerosis (PwMS) experienced changes in health behaviors and access to MS care due to the COVID-19 pandemic. The USA has the highest recognized number of Covid19 infections globally. The extent of the impact of COVID-19 has not been well characterized in large samples of PwMS to date. The MS patient perspective on COVID-19 would complement the physician-reported cases of MS and COVID-19 in the literature. Methods A cross-sectional survey of adult PwMS was performed online, using the U.S.-based patient-powered iConquerMS™ platform, in April 2020. Results There were 1,145 respondents (response rate: 20%). 1,019 had a diagnosis of MS and responded completely (average age: 54.2 years, range: 20-81; 79% female; 64% relapsing remitting, 22% secondary progressive, 12% primary progressive; 88% in the USA). 748 (73%) used a DMT in the last year, primarily higher-efficacy therapies: ocrelizumab (n=238), dimethyl fumarate (n=85), fingolimod (n=80). The most frequent comorbidities were depression (41%), hypertension (26%), and asthma (12%). Women were more worried than men about COVID-19 (p=0.001); non-white-identifying PwMS believed it was a greater danger to their health than white-identifying PwMS (p=0.002). Through the continuum of symptoms to care, 61% of PwMS (n=617) reported symptoms associated with COVID-19, 39% (n=395) knew someone exposed to COVID-19, 4% (n=38) were aware of a personal COVID-19 exposure, 13% (n=128) wanted testing for COVID-19 but could not access it, and 4% (n=43) were tested. Specific to their MS care, 64% (n=650) canceled a medical visit, 22% (n=222) canceled a neurologist visit, 11% (n=112) canceled an MRI, 21% (n=212) canceled a laboratory test, and 10% (n=98) changed their DMT in some way due to COVID19 including 65 delaying at least one dose. 37% (n=382) had a telehealth visit due to COVID-19. 37% of PwMS (n=374) experienced employment changes, most commonly working from home (n=194) and having work hours reduced (n=65) while 32 lost their jobs. Of the 7 cases who tested positive for COVID-19 (

Made available in DSpace on 2020-12-12T02:15:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Multiple Sclerosis International Federation Background: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. Objectives: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. Methods: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. Results: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. Conclusions: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS. Biomedical Research Institute and Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Göttingen MS International Federation ESAT-STADIUS KU Leuven Biomedical Research Institute and Data Science Institute Hasselt University Diepenbeek Belgium/ESAT-STADIUS KU Leuven Clinical Outcomes Research (CORe) Unit The University of Melbourne Department of Neurology CHU Pontchaillou Neuroepidemiology Unit Melbourne School of Population Global Health The University of Melbourne Department of Computer Science and Leuven.AI KU Leuven QMENTA Department of Clinical Neuroscience Swedish MS Registry iConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData MS Forschungs- und Projektentwicklungs-gGmbH UK MS Register COViMS St Louis USA/ Division of Biostatistics Washington University in St. Louis COViMS USA/National Multiple Sclerosis Society Neurology Department Hospital Universitario de CEMIC MSBase Registry Department of Neuroscience Central Clinical School Monash University The Australian MS Longitudinal Study (AMSLS) Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset LEOSS Department of Neurology Katholisches Klinikum Bochum Brazilian Multiple Sclerosis Association (ABEM) Cleveland Clinic MS COVID-19 Registry Mellen MS Center Cleveland Clinic Icometrix – Icompanion OptimiseMS Preventive Neurology Unit Queen Mary University of London The Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista (Unesp) Faculdade de Medicina Botucatu/REDONE – Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders RELACOEM Mental Health Area EMA MS and Demyelinating Diseases Hospital Británico de Buenos Aires – EMA Department of Neurology Strasbourg University Hospital COVISEP Institute of Experimental Neurology Ospedale San Raffaele Melbourne MS Centre Department of Neurology Royal Melbourne Hospital Institut du Cerveau ICM APHP – Hôpital Pitié Salpêtrière Sorbonne University Menzies Institute for Medical Research University of Tasmania Imperial College London Swansea University Multiple Sclerosis University Center Ramos Mejia Hospital – EMA Universidade Estadual Paulista (Unesp) Faculdade de Medicina Botucatu/REDONE – Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

Background Risk factors for COVID-19 infection among people with multiple sclerosis (PwMS) remain unconfirmed. While biological, socioeconomic and clinical risk factors have been identified among the general population, a comprehensive assessment of risk factors for COVID-19 infection among PwMS is lacking. Methods A survey assessing personal experiences with COVID-19 in the USA was distributed online via the iConquerMS platform from December 18, 2020 to February 10, 2021. We conducted a retrospective nested case–control study of PwMS who self-reported testing positive for COVID-19 versus not. Risk factors evaluated include age, occupational setting, social determinants of health index, physical disability via Patient-Determined Disease Steps, disease-modifying therapy (DMT) and progressive disease. Results Of 611 PwMS, 47 (7.7%) self-reported a positive COVID-19 test. DMT use (odds ratio [95% CI]: 2.10 [0.75–5.39]) and employment outside the home (2.79 [1.42–5.41]) increased risk of COVID-19 infection, while older age (0.97 [0.95–0.99]), increased disability (0.81 [0.69–0.94]) and progressive disease (0.42 [0.19–0.86]) decreased risk in univariate analyses. No risk factor remained significant in the multivariate model. Of the 47 PwMS with a positive test, seven were admitted to the hospital, of whom two required intensive care. Forty-three (91.5%) experienced common COVID-19 symptoms, and 23 (48.9%) reported concurrent new/worsening neurological symptoms. Conclusion The prevalence of COVID-19 infection in this online study of PwMS approximated the US population's prevalence. When incorporating biological, socioeconomic and clinical risk factors for COVID-19, we did not find any independent risk factors for infection among PwMS in the USA.

Background We propose a Phase III trial that compares the effectiveness of an exercise training program delivered in a facility-based setting with direct, in-person supervision or a home-based setting with remote supervision via telerehabilitation for improving walking performance in persons with multiple sclerosis(MS) who have walking dysfunction and mobility disability. Methods/design The study was developed with stakeholder engagement and is a multi-site trial that follows a 2-stage, randomized choice design. The trial compares the effectiveness of a 16-week evidence-based, individualized exercise program delivered in a supervised, facility-based setting versus a remotely coached/guided, home-based setting using telerehabilitation in physically inactive and cognitively intact people with MS who have walking dysfunction and mobility disability(N = 500). The primary outcome is walking speed. The secondary outcomes are walking endurance, disability status, and patient-reported outcomes of physical activity, walking impairment, fatigue, and quality of life. The components of the exercise program itself are similar between the groups and follow the Guidelines for Exercise in MS protocol. This includes a program manual, exercise prescription, exercise equipment, social-cognitive theory materials including newsletters, logs, and calendars, and one-on-one behavioral coaching by exercise specialists with background in MS. The main difference between groups is the coaching approach and setting for delivering the exercise training program. The outcomes will be collected by treatment-blinded assessors at baseline(week 0), mid-intervention(week 8), post-intervention(week 16), and follow-up(week 52). Discussion The proposed study will provide evidence for the effectiveness of a novel, widely-scalable program for delivering exercise training in persons with MS who have walking dysfunction and mobility disability.

Background Previous infection with Epstein–Barr virus (EBV) and a history of infectious mononucleosis (IM) have been previously associated with an increased risk of multiple sclerosis (MS). Whether there are common genetic factors that may partially explain these associations has not been thoroughly explored. Objective To investigate whether select polymorphisms in genes associated with IM susceptibility are related to MS risk—a self-reported history of IM or antibody titer against Epstein–Barr virus nuclear antigen 1 (anti-EBNA1). Methods A case-control study including 1213 MS cases and 454 controls enrolled in the Accelerated Cure Project for MS (ACP) Repository. Select polymorphisms in HLA-A, SH2D1A and IL15RA and anti-EBNA1 Ab titers were measured using stored blood samples provided by participants. Generalized linear models were used to assess the associations between select polymorphisms and odds of MS, odds of IM or anti-EBNA1 Ab titers. Results No significant associations were observed between the selected polymorphisms and odds of MS, odds of IM or anti-EBNA1 Ab titer. Conclusion It is unlikely that any of the studied polymorphisms contribute to the explaining the association between anti-EBNA1 Ab titer or history of IM and MS.

Persons with Multiple Sclerosis (MS) have a life expectancy 6–7 years less than those without the disease, but disability increases with disease duration and often limits ability to work. Access to personal insurance, including health (HI), short- and long-term disability income (STD, LTD), long-term care (LTC), and life insurance (LI), is largely employer-based or purchased out of pocket from earnings. Maintaining or losing employment can cause concern regarding the cost and coverage of insurance, especially for those over 50 years of age, for whom keeping employment may be challenging at best.

There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. Anti-aquaporin-4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO), but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre-analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease.

Data science plays an increasingly important role in solving today's scientific and social challenges. To promote progress toward a cure for multiple sclerosis, the Accelerated Cure Project has created an open repository of biological and survey data on patients with multiple sclerosis. Similar large-scale repositories are being created in other domains. As the open, data-driven model of science proliferates, the research community faces a growing need for a cloud platform for collaborative data science. Such a platform should facilitate collaboration between domain experts and data scientists and possess artificial intelligence capabilities for organizing, recommending, and manipulating data analyses. In this paper, we present some foundational technologies motivated by this vision. Our system automatically extracts a high-level dataflow graph from a data analysis. This graph describes how data flows through an analysis pipeline, including which statistical methods are used and how they fit together. The system requires no special annotations from the data analyst and consumes analyses written in Python using standard tools, such as Scikit-learn and Statsmodels. In this paper, we explain how our system works and how it fits into our larger vision for a collaborative data science platform.

There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process. In this article, we argue that new standards are necessary in order to enable important pragmatic clinical research while at the same time protecting patients’ rights and interests.

There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.

An association between multiple sclerosis (MS) and the human leukocyte antigen (HLA) complex, a dense cluster of genes on the short arm of chromosome 6, was first noted over 30 years ago. In Caucasian populations of Northern European descent, the DR15 haplotype (DRB1*1501-DQA1*0102-DQB1*0602) has been hypothesized to be the primary HLA genetic susceptibility factor for MS. However, studies of other populations have produced varying results. Thus, the authors reviewed the literature for articles on the association between the DR15 haplotype and MS. They identified 72 papers meeting the inclusion criteria: human genetic studies written in English that were published between 1993 and 2004 and that reported allele frequencies for HLA-DRB1*1501, HLA-DQA1*0102, or HLA-DQB1*0602 or the frequency of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype. Most of the studies identified used a case-control design (n = 60), while the remainder used a family-based design (n = 22). In most of these papers, investigators reported a higher frequency of the DR15 haplotype and/or its component alleles among MS cases than among controls. However, the authors' confidence in these results is tempered by factors related to study design that may have biased the outcomes.

Objective: Explore association between gMS-Classifier1 status and risk for fast progression to EDSS≥4.0 in RRMS patients. Background Positive gMS-Classifier1 serum immunoassay, based on IgM antibodies against glycan antigens (anti-GAGA panel) was associated with fast progression by EDSS≥1.0 point in the accelerated cure project (ACP) RRMS cohort. We have further explored its association with fast progression to EDSS≥4.0 on an extended ACP cohort. Design/Methods: Selection criteria for frozen sera from ACP: Two EDSS records separated by ≥6 months, first available EDSS record Results: Selection criteria were met by 120 patients, median (IQR) EDSS at first and second visits were 1.5 (1.5-2.0) and 2.0 (1.5-2.5), respectively. Median (IQR) time between first and second records was 1050 (473-1958) days. The 75-percentile time to progress to EDSS≥4.0 was significantly faster for gMS-Classifier1 positive patients (n=36, 2000 days) than negative patients (n=84, did not reach 75-percentiles, HR 11.8 95%CI 1.6-88.7, p=0.005 log-rank). gMS-Classifer1 (HR 13.0, 95%CI 1.3-127.6) and duration of disease (HR 0.66, 95%CI 0.44-0.99) were the only variables staying in the Cox model (p-value=0.0003). Similar associations were found for faster progression to EDSS≥3.0 (HR 3.5, 95%CI 1.2-10.1 p-value=0.02) and for fast progression by EDSS≥1.0 point (HR 4.2, 95%CI 1.3-14.0 p-value=0.02). Conclusions: In this retrospective analysis of RRMS patients, gMS-Classifier1 positive status was an independent variable for association with faster disability progression to EDSS≥4.0. A prospective analysis is required to verify the predictive value of this association. Supported by: Glycominds. Disclosure: Dr. Yarden has received personal compensation for activities with Glycominds Ltd. Dr. Yarden holds stock and/or stock options in Glycominds. Dr. Schmidt has nothing to disclose. Ms. Spector has received personal compensation for activities with Glycominds Ltd as an employee. Ms. Spector holds stock and/or stock options in Glycominds Ltd. Mr. Rimer has received personal compensation for activities with Glycominds as an employee. Dr. Loud has nothing to disclose. Dr. Dotan has received personal compensation for activities with Glycominds Ltd. as an employee.Dr. Dotan holds stock and/or stock options in Glycominds Ltd., which sponsored research in which Dr. Dotan was involved as an investigator.