Disease Activity In Multiple Sclerosis Research Articles

Neurofilament Light Chains: A Reliable Biomarker of Disease Activity in MS

Background: In this study, we aim (1) to highlight the role of multiple sclerosis (MS) non radiological biomarkers in establishing prognostic value of disease activity in CIS and in monitoring disease activity in relapsing remitting multiple sclerosis (RRMS), and (2) to establish the value of quantification of neurofilament (nfl) light chains in progressive multiple sclerosis in relation to active disease and chronic stable disease.

Multiple Sclerosis Disease Activity and Disability Following Discontinuation of Natalizumab for Pregnancy

The magnitude of risk of pregnancy-related multiple sclerosis relapses, particularly severe relapses, following natalizumab cessation is unclear, as is whether this risk is reduced by pregnancy or other modifiable factors. To determine the association of early natalizumab withdrawal before or during pregnancy with risk of severe relapses and relapse-related disability. This prospective cohort study used data from the German Multiple Sclerosis and Pregnancy Registry, which enrolled participants between November 2006 and February 2018. Data were collected through structured telephone-administered questionnaires and review of neurologists' notes. Registry patients who stopped natalizumab treatment within the 2 years before or in the first trimester of pregnancy were included in this analysis. Data were analyzed between January and November 2021. Cessation of natalizumab before pregnancy or until the first trimester. Severe and significant relapse-related disability was defined as at least a 2.0-point increase on the expanded disability status scale or new or worsening relapse-related ambulatory impairment. Multivariable models accounting for measures of disease severity and repeated events were used. The cohort comprised 255 women with 274 pregnancies (mean [SD] age at pregnancy onset, 31.25 [4.27] years) who stopped natalizumab before pregnancy (n = 85; median time before last menstrual period, 14.29 weeks [IQR, 3.14-42.43 weeks]) or in the first trimester (n = 189). During pregnancy and the postpartum year, relapses were reported in 183 pregnancies (66.78%), severe relapses in 44 pregnancies (16.05%), and potentially life-threatening relapses in 3 pregnancies (1.10%). One year post partum, significant relapse-related disability was accrued in 29 pregnancies (10.58%). Relapses during pregnancy (n = 109; 39.78%) and in the postpartum period (n = 135; 49.27%) were common. Pregnancy (as a time-dependent covariate) was not associated with a reduced relapse risk (adjusted HR, 0.90; 95% CI, 0.64-1.27). Neither exclusive breastfeeding (adjusted HR, 1.34; 95% CI, 0.86-2.10) nor restarting natalizumab within 4 weeks post partum (adjusted HR, 1.06; 95% CI, 0.48-2.36) were associated with a reduced risk of early postpartum relapses 6 months after delivery. However, the relapse rate ratio during 12 months post partum was lower (0.49; 95% CI, 0.28-0.86) when natalizumab was restarted in the first 4 weeks after birth. This cohort study's finding suggest that 10% of women may retain clinically meaningful disability from pregnancy-related natalizumab cessation relapses 1 year post partum. This information should be shared with women on natalizumab who desire pregnancy to weigh the high risk of pregnancy-related relapses and disability to the partly uncertain risks of continuing natalizumab throughout pregnancy or switching to depleting agents before conception.

High or increasing serum NfL is predictive of impending multiple sclerosis relapses

BackgroundOne-off serum levels of neurofilament light chain (sNfL) is an established predictor of emerging disease activity in multiple sclerosis (MS). However, the importance of longitudinal increases in sNfL is yet to be enumerated, an important consideration as this test is translated for serial monitoring. Glial Fibrillary Acidic Protein (sGFAP) is another biomarker of predictive interest. Our objective was to assess the association between longitudinal changes sNfL and prediction of future relapses, as well as a possible role for sGFAP. MethodsParticipants with active MS were prospectively monitored for one year as part of a clinical trial testing mesenchymal stem cells. Visits every three months or less included clinical assessments, MRI scans and serum draws. sNfL and sGFAP concentrations were quantified with Single Molecule Array immunoassay. We used Kaplan-Meier estimates and Anderson-Gill Cox regression models with and without adjustment for age, sex, disease subtype, disease duration and expanded disability status score (EDSS) to estimate the rate of relapse predicted by baseline and longitudinal changes in biomarker. Results58 Canadian and Italian participants with MS were enrolled in this study. Higher baseline sNfL was future relapse (Log-rank p = 0.0068), MRI lesions (p=0.0096), composite-relapse associated worsening (p=0.01) and progression independent of relapse activity (p=0.0096). Conversely, baseline sGFAP was only weakly associated with MRI lesions (0.044). Cross-sectional analyses of baseline sNfL revealed that a two-fold difference in baseline sNfL, e.g. from 10 to 20 pg/mL, was associated with a 2.3-fold increased risk of relapse during follow-up (95% confidence interval 1.65–3.17). Longitudinally, a two-fold increase in sNfL level from the first measurement was associated with an additional 1.46 times increased risk of relapse (1.07–2.00). The impact of longitudinal increases in sNfL on the risk of relapse were most pronounced for patients with lower baseline values of sNfL (<10 pg/mL: HR = 1.54, 1.06–2.24). These associations remained significant after adjustment for potential confounders. ConclusionWe enumerate the risk of relapse associated with dynamic changes in sNfL. Both baseline and longitudinal change in sNfL may help identify patients who would benefit from early treatment optimisation. Trial registrationsCanada:NCT02239393, Italy:NCT01854957&EudraCT, 2011–001295-19 Classification of evidenceThis study provides class 1 evidence that high baseline and longitudinal increases in sNfL are predictive of impending relapses in patients with active MS.

Vitamin D and Depressive Symptoms in Adults with Multiple Sclerosis: A Scoping Review

Background. Vitamin D deficiency has been correlated with Multiple Sclerosis (MS) risk and disease activity. There is some controversy as to whether vitamin D could have an impact on depressive symptoms in people with MS (pwMS). The aim of this scoping review was to evaluate the association between vitamin D status and depressive symptoms in pwMS. Methods. We searched databases to include studies published up to March 2021 to provide an overview of the available evidence on the correlation between vitamin D status and depressive symptoms in pwMS. The eligibility criteria were as follows: studies evaluating the use of vitamin D measurement on depressive symptoms in patients suffering from MS, including randomized and non-randomized studies; studies written in English; and studies exploring an adult population over the age of 18. Results. Eleven studies met our inclusion criteria: two of them were abstracts only; the majority were cross-sectional studies; two were prospective longitudinal studies; one was a retrospective cohort study; and one was a randomized placebo-controlled trial (RCT). Of the eleven studies selected, seven showed a potential correlation between low vitamin D levels and depressive symptoms. Conclusion. Future RCT studies should include patients with greater severity of depressive symptoms and should consider confounding factors such as sun exposure and seasonal variation of vitamin D.

NK Cells and Innate-Like T Cells After Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which autoreactive T and B cells play important roles. Other lymphocytes such as NK cells and innate-like T cells appear to be involved as well. To name a few examples, CD56bright NK cells were described as an immunoregulatory NK cell subset in MS while innate-like T cells in MS were described in brain lesions and with proinflammatory signatures. Autologous hematopoietic stem cell transplantation (aHSCT) is a procedure used to treat MS. This procedure includes hematopoietic stem/progenitor cell (HSPC) mobilization, then high-dose chemotherapy combined with anti-thymocyte globulin (ATG) and subsequent infusion of the patients own HSPCs to reconstitute a functional immune system. aHSCT inhibits MS disease activity very effectively and for long time, presumably due to elimination of autoreactive T cells. Here, we performed multidimensional flow cytometry experiments in peripheral blood lymphocytes of 27 MS patients before and after aHSCT to address its potential influence on NK and innate-like T cells. After aHSCT, the relative frequency and absolute numbers of CD56bright NK cells rise above pre-aHSCT levels while all studied innate-like T cell populations decrease. Hence, our data support an enhanced immune regulation by CD56bright NK cells and the efficient reduction of proinflammatory innate-like T cells by aHSCT in MS. These observations contribute to our current understanding of the immunological effects of aHSCT in MS.

Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study.

Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their possible role in MS. To evaluate the correlation between innate and adaptive immune cell subsets and disease activity in MS in the context of treatment with alemtuzumab. A two-center observational cohort of patients treated with alemtuzumab underwent immune profiling of T, B, and natural killer (NK) cells, biomarker, clinical and radiological follow-up. After treatment, the percentage of NK and B cells increased; NK, T- and B-cell populations underwent a profound rearrangement. Within the effector T-cell compartment, treatment led to a transient decrease, followed by an increase, of T-helper 1 cells, and to a transient decrease of T-helper 17 cells. Within the T-regulatory compartment, naïve T-regulatory cells increased. Within the B-cell compartment, memory B cells and mature B cells decreased, whereas transitional B cells increased. Within the NK cell compartment, CD56bright NK cells increased. Subjects without disease activity had a greater decrease in serum NfL and greater NK cell/CD3+ T cell ratio. NK cell numbers at baseline and after treatment influenced reconstitution of T and B cells, being inversely correlated with the reconstitution of proinflammatory CD3+ T cells and mature B cells, and directly correlated to the increase in transitional B cells. The results of this study provide novel evidence that NK cells influence reconstitution of adaptive immune cells upon alemtuzumab and that patients with a successful response to alemtuzumab have an early immune reconstitution dominated by NK cells.

Health Economic Impact of Software-Assisted Brain MRI on Therapeutic Decision-Making and Outcomes of Relapsing-Remitting Multiple Sclerosis Patients-A Microsimulation Study.

Aim: To develop a microsimulation model to assess the potential health economic impact of software-assisted MRI in detecting disease activity or progression in relapsing-remitting multiple sclerosis (RRMS) patients. Methods: We develop a simulated decision analytical model based on a hypothetical cohort of RRMS patients to compare a baseline decision-making strategy in which only clinical evolution (relapses and disability progression) factors are used for therapy decisions in MS follow-up, with decision-making strategies involving MRI. In this context, we include comparisons with a visual radiologic assessment of lesion evolution, software-assisted lesion detection, and software-assisted brain volume loss estimation. The model simulates clinical (EDSS transitions, number of relapses) and subclinical (new lesions and brain volume loss) disease progression and activity, modulated by the efficacy profiles of different disease-modifying therapies (DMTs). The simulated decision-making process includes the possibility to escalate from a low efficacy DMT to a high efficacy DMT or to switch between high efficacy DMTs when disease activity is detected. We also consider potential error factors that may occur during decision making, such as incomplete detection of new lesions, or inexact computation of brain volume loss. Finally, differences between strategies in terms of the time spent on treatment while having undetected disease progression/activity, the impact on the patient’s quality of life, and costs associated with health status from a US perspective, are reported. Results: The average time with undetected disease progression while on low efficacy treatment is shortened significantly when using MRI, from around 3 years based on clinical criteria alone, to 2 when adding visual examination of MRI, and down to only 1 year with assistive software. Hence, faster escalation to a high efficacy DMT can be performed when MRI software is added to the radiological reading, which has positive effects in terms of health outcomes. The incremental utility shows average gains of 0.23 to 0.37 QALYs over 10 and 15 years, respectively, when using software-assisted MRI compared to clinical parameters only. Due to long-term health benefits, the average annual costs associated with health status are lower by $1500–$2200 per patient when employing MRI and assistive software. Conclusions: The health economic burden of MS is high. Using assistive MRI software to detect and quantify lesions and/or brain atrophy has a significant impact on the detection of disease activity, treatment decisions, health outcomes, utilities, and costs in patients with MS.

Smartphone-derived keystroke dynamics are sensitive to relevant changes in multiple sclerosis.

BackgroundTo investigate smartphone keystroke dynamics (KD), derived from regular typing, on sensitivity to relevant change in disease activity, fatigue, and clinical disability in multiple sclerosis (MS).MethodsPreplanned interim analysis of a cohort study with 102 MS patients assessed at baseline and 3‐month follow‐up for gadolinium‐enhancing lesions on magnetic resonance imaging, relapses, fatigue and clinical disability outcomes. Keyboard interactions were unobtrusively collected during typing using the Neurokeys App. From these interactions 15 keystroke features were derived and aggregated using 16 summary and time series statistics. Responsiveness of KD to clinical anchor‐based change was assessed by calculating the area under the receiver operating characteristic curve (AUC). The optimal cut‐point was used to determine the minimal clinically important difference (MCID) and compared to the smallest real change (SRC). Commonly used clinical measures were analyzed for comparison.ResultsA total of 94 patients completed the follow‐up. The five best performing keystroke features had AUC‐values in the range 0.72–0.78 for change in gadolinium‐enhancing lesions, 0.67–0.70 for the Checklist Individual Strength Fatigue subscale, 0.66–0.79 for the Expanded Disability Status Scale, 0.69–0.73 for the Ambulation Functional System, and 0.72–0.75 for Arm function in MS Questionnaire. The MCID of these features exceeded the SRC on group level. KD had higher AUC‐values than comparative clinical measures for the study outcomes, aside from ambulatory function.ConclusionsKeystroke dynamics demonstrated good responsiveness to changes in disease activity, fatigue, and clinical disability in MS, and detected important change beyond measurement error on group level. Responsiveness of KD was better than commonly used clinical measures.

The effects of HMG-CoA reductase inhibitors on disease activity in multiple sclerosis: A systematic review and meta-analysis

ObjectiveTo assess whether statins (3‑hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert disease-modifying effects in multiple sclerosis (MS). ApproachA systematic review and meta-analysis was performed including randomized-controlled clinical trials (RCTs) on statin use in MS. A random-effects model was applied to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), when comparing patients treated with statins alone or adjunct to disease modifying treatment (DMT) to non-statin-treated patients. ResultsWe identified 7 RCTs including 789 patients with relapsing-remitting MS (RRMS), all of whom received additional DMT with IFN-β. Single identified RCTs in secondary-progressive MS (SPMS), clinically isolated syndrome (CIS) and optic neuritis (ON) were not meta-analyzed. In RRMS, add-on statin use was not associated with the risk of clinical relapse (OR=1.30, 95%CI: 0.901.87) or EDSS-progression from baseline, neither appeared related to the risk of new contrast-enhancing or T2 lesions (OR=1.28, 95%CI: 0.364.58), and the risk of whole-brain volume reduction on MRI. Add-on statins to IFN-β were safe and well-tolerated. In SPMS, stand-alone simvastatin led to significantly reduced annualized rate of whole-brain volume reduction. In CIS and ON, statins were associated with reduced risk for new T2 lesions and improved visual recovery, respectively. ConclusionsWe detected no benefit from statin treatment as add-on to IFN-β in RRMS. However, a potential beneficial effect in SPMS, CIS and ON deserves independent confirmation and further evaluation within adequately powered RCTs.

The wearing-off phenomenon of ocrelizumab in patients with multiple sclerosis

BackgroundPatients with multiple sclerosis (MS) who are treated with monoclonal antibodies frequently report an increase of MS-related symptoms prior to the next dose known as the wearing-off phenomenon. The objective of this study was to assess the prevalence and predicting factors of the wearing-off phenomenon in patients with MS using ocrelizumab. MethodsThis was a prospective cohort study in patients with MS receiving ocrelizumab ≥1 year. Most participants received B-cell guided personalized extended interval dosing to limit ocrelizumab exposure and hospital visits during the COVID-19 pandemic (cut-off ≥ 10 cells/µL). Participants completed questionnaires during ocrelizumab infusion and 2 weeks thereafter. Demographics, clinical and radiological characteristics, CD19 B-cell counts, and serum neurofilament light (sNfL) levels were collected. Data were analyzed using logistic regression analyses. ResultsSeventy-one (61%) out of 117 participants reported the wearing-off phenomenon during ocrelizumab treatment. The most frequently reported symptoms were fatigue, cognitive disability and sensory symptoms. Wearing-off symptoms started < 1 week (11%), 1–4 weeks (49%) or more than 4 weeks (37%) before ocrelizumab infusion. Fifty participants (43%) reported a current wearing-off phenomenon at the first questionnaire. Higher body mass index (threshold BMI ≥ 25) increased the odds of reporting a current wearing-off phenomenon (OR 2.70, 95% CI 1.26 to 5.80, p = .011). Infusion interval, EDSS score, MRI disease activity, clinical relapses, CD19 B-cell counts, and sNfL levels were no predictors. Disappearance of the wearing-off phenomenon occurred in the first week after ocrelizumab infusion in most participants. Participants with a current wearing-off phenomenon significantly improved in self-reported physical and psychological functioning after ocrelizumab infusion. Reporting the wearing-off phenomenon did not influence treatment satisfaction. Forty of 109 participants (37%) reported post-infusion symptoms, such as fatigue, flu-like symptoms or walking difficulties. These post-infusion symptoms started directly or in the first week after ocrelizumab infusion and disappeared within 2 weeks. ConclusionsThe wearing-off phenomenon is reported by more than half of patients with MS using ocrelizumab. Only BMI was identified as a predicting factor. The wearing-off phenomenon was not elicited by extending infusion intervals or higher B-cell counts. The wearing-off phenomenon of ocrelizumab therefore does not seem to reflect suboptimal control of MS disease activity.

Temporal trends of multiple sclerosis disease activity: Electronic health records indicators

BackgroundLong-term data on multiple sclerosis (MS) inflammatory disease activity are limited. We examined electronic health records (EHR) indicators of disease activity in people with MS. MethodsWe analyzed prospectively collected research registry data and linked EHR data in a clinic-based cohort from 2000 to 2016. We used the trend of the yearly incident relapse rate from the registry data as benchmark. We then calculated the temporal trends of potentially relevant EHR measures, including mean count of the MS diagnostic code, mentions of MS-related concepts, MS-related health utilizations and selected prescriptions. Results1,555 MS patients had both registry and EHR data. Between 2000 and 2016, the registry data showed a declining trend in the yearly incident relapse rate, parallel to an increasing trend of DMT usage. Among the EHR measures, covariate-adjusted frequency of diagnostic code of MS, procedure codes of MS-related imaging studies and emergency room visits, and electronic prescription for steroids declined over time, mirroring the temporal trend of the benchmark yearly incident relapse rate. ConclusionThis study highlights EHR indicators of MS relapse that could enable large-scale examination of long-term disease activities or inform individual patient monitoring in clinical settings where EHR data are available.

Vitamin D in Multiple Sclerosis-Lessons From Animal Studies.

Multiple sclerosis is a multifactorial disease of the central nervous system with both genetic and environmental causes. The exact disease mechanisms are still unclear. Consequently, studies of possible treatment and preventive measures cover a large setting of heterogeneous approaches. Vitamin D is one of these approaches, and in many trials the relation of vitamin D serum levels and multiple sclerosis disease risk and activity describes different effects with sometimes inconsistent findings. Animal models are substantial for the research of disease mechanisms, and many of the drugs that are currently in use in multiple sclerosis have been developed, tested, or validated via animal studies. Especially when clinical studies show contradicting findings, the use of standardized settings and information about the mechanistic background is necessary. For this purpose, animal models are an essential tool. There is a variety of different experimental settings and types of animal models available, each of them with own strengths but also weaknesses. This mini-review aims to overview results of vitamin D studies in different animal models and sums up the most important recent findings.

Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series.

(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing–remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

Background: The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective: To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Methods: We analyzed 369 blood samples from 155 early relapsing-remitting MS patients on interferon beta-1a. We compared disease activity, including the rate of brain volume loss in subgroups defined by NEDA-3 status and high or low sNfL (> 90th or < 90th percentile). Results: In patients with disease activity (EDA-3), those with higher sNFL had higher odds of EDA-3 in the following year than those with low sNFL (86.5% vs 57.9%; OR = 4.25, 95% CI: [2.02, 8.95]; p = 0.0001) and greater whole brain volume loss during the following year (β = −0.36%; 95% CI = [−0.60, −0.13]; p = 0.002). Accordingly, NEDA-3 patients with high sNfL showed numerically higher disease activity (EDA-3) in the following year compared with those with low sNfL (57.1% vs 31.1%). Conclusion: sNfL improves the ability to identify patients at higher risk of future disease activity, beyond their NEDA-3 status. Measurement of sNfL may assist clinicians in decision-making by providing more sensitive prognostic information.

COVID-19 in multiple sclerosis: Experience from North India

Background: Multiple Sclerosis (MS) patients on disease modifying therapies may be at risk of infection related to novel coronavirus disease (COVID-19) pandemic. Data on COVID 19 infections in Indian MS patients has not been well described Objective: To determine the clinical characteristics and outcome in MS patients on disease modifying therapies (DMTs) affected with COVID-19 and to assess the influence of COVID-19 infection on Multiple Sclerosis disease activity.

A Novel Digital Care Management Platform to Monitor Clinical and Subclinical Disease Activity in Multiple Sclerosis.

In multiple sclerosis (MS), the early detection of disease activity or progression is key to inform treatment changes and could be supported by digital tools. We present a novel CE-marked and FDA-cleared digital care management platform consisting of (1) a patient phone/web application and healthcare professional portal (icompanion) including validated symptom, disability, cognition, and fatigue patient-reported outcomes; and (2) clinical brain magnetic resonance imaging (MRI) quantifications (icobrain ms). We validate both tools using their ability to detect (sub)clinical disease activity (known-groups validity) and real-world data insights. Surveys showed that 95.6% of people with MS (PwMS) were interested in using an MS app, and 98.2% were interested in knowing about MRI changes. The icompanion measures of disability (p < 0.001) and symptoms (p = 0.005) and icobrain ms MRI parameters were sensitive to (sub)clinical differences between MS subtypes. icobrain ms also decreased intra- and inter-rater lesion count variability and increased sensitivity for detecting disease activity/progression from 24% to 76% compared to standard radiological reading. This evidence shows PwMS’ interest, the digital care platform’s potential to improve the detection of (sub)clinical disease activity and care management, and the feasibility of linking different digital tools into one overarching MS care pathway.

К ПРОБЛЕМЕ СВЯЗИ ИММУНОТЕРАПИИ У ПАЦИЕНТОВ, СТРАДАЮЩИХ РЕЦИДИВИРУЮЩИМ РАССЕЯННЫМ СКЛЕРОЗОМ, С РИСКОМ ТЯЖЕЛОГО ТЕЧЕНИЯ COVID-19

Immunomodulatory drugs are important to control disease activity in relapsing-remitting multiple sclerosis (MS). Anti-CD 20-therapy is one of such medications. In Sweden, extensive off label prescription of rituximab (RTX) in MS has been documented; it is presently prescribed for more than half of all treated MS patients. The rationale for the increasing prescription of RTX was previous data from phase II and observational studies supporting high efficacy and safety, in addi- tion to the financial aspect. We report national data on usage of disease modifying therapies in MS patients and risk of se- vere COVID-19 in association with RTX exposure within this group. The Swedish National MS Registry (SMSreg) aims to cover all patients with MS in the country, (n=approximately 18,000). After COVID-19 pandemic started in Sweden, a new section was established in it to register clinical and demo- graphic parameters in COVID-19-infected patients. Data presented in the current report were obtained from the SMSreg. A total of 85 out of approximately 6,000 RTX-treated Swedish MS patients had been hospitalized with COVID-19 (as re- ported from the SMSreg, June 16, 2021) and adjusted analyses showed a 2–3 fold increase in a risk (OR = 2.89; p = 0.001) of hospitalization for anti-CD20 treated patients. A change of praxis was introduced in Sweden in spring 2020, resulting in a ma- jority of patients receiving RTX infusions with extended intervals in order to reduce the risk of severe COVID-19 infection. Current Swedish registry data suggest that exposure to RTX in MS may affect the clinical outcome of COVID-19 infec- tion. These observations have rapidly impacted use of immunomodulatory drugs in Swedish MS patients.

THE RISK OF COVID-19 SEVERITY IN PATIENTS WITH MS APPEARS TO BE ASSOCIATED WITH IMMUNOTHERAPY

Immunomodulatory drugs are important to control disease activity in relapsing-remitting multiple sclerosis (MS). Anti-CD 20-therapy is one of such medications. In Sweden, extensive off label prescription of rituximab (RTX) in MS has been documented; it is presently prescribed for more than half of all treated MS patients. The rationale for the increasing prescription of RTX was previous data from phase II and observational studies supporting high efficacy and safety, in addi- tion to the financial aspect. We report national data on usage of disease modifying therapies in MS patients and risk of se- vere COVID-19 in association with RTX exposure within this group. The Swedish National MS Registry (SMSreg) aims to cover all patients with MS in the country, (n=approximately 18,000). After COVID-19 pandemic started in Sweden, a new section was established in it to register clinical and demo- graphic parameters in COVID-19-infected patients. Data presented in the current report were obtained from the SMSreg. A total of 85 out of approximately 6,000 RTX-treated Swedish MS patients had been hospitalized with COVID-19 (as re- ported from the SMSreg, June 16, 2021) and adjusted analyses showed a 2–3 fold increase in a risk (OR = 2.89; p = 0.001) of hospitalization for anti-CD20 treated patients. A change of praxis was introduced in Sweden in spring 2020, resulting in a ma- jority of patients receiving RTX infusions with extended intervals in order to reduce the risk of severe COVID-19 infection. Current Swedish registry data suggest that exposure to RTX in MS may affect the clinical outcome of COVID-19 infec- tion. These observations have rapidly impacted use of immunomodulatory drugs in Swedish MS patients.

197Assessment of Depression, Anxiety and Fatigue in relation to diet quality in Multiple Sclerosis

Abstract Background Many people with multiple sclerosis (MS) modify their dietary intake, but there is low evidence that this influences MS disease activity or progression. We examined whether indices of diet quality (Dietary Quality Tracker and Australian Recommended Food Score) were associated with depression, anxiety and fatigue using a prospective cohort. Methods The Auslong Study participants were followed annually for 10 years (n = 223 with MS at 10 years). Depression &amp; anxiety (Hospital Anxiety &amp; Depression Scale, HADS) and fatigue (Fatigue Severity Scale) were assessed at the 5th and 10th-year reviews. Dietary intake in the preceding 12 months using the Cancer Council Victoria Food Frequency Questionnaire was assessed at the baseline, 5th and 10th year reviews. Results Overall diet quality at the 5th-year review was not associated with a change in depression, anxiety or fatigue in the subsequent 5 years. However, a higher intake of protein, grain and discretionary foods at the 5th-year review using the Dietary Quality Tracker were associated with an increase in HADS depression score over the subsequent 5 years (e.g. highest vs lowest quartile protein: β=2.14,95%CI=0.91,3.37,p&amp;lt;0.001). Also, a higher legume intake at the 5th-year review was associated with a decrease in HADS anxiety score over the subsequent 5 years( e.g. highest vs lowest quartile: β=-1.92,95%CI=-3.32,-0.53,p=0.01). Conclusion Overall diet quality was not associated with a subsequent change in depression, anxiety or fatigue over 5-years but some specific food groups were associated with depression and anxiety. Replication is required before testing these findings with diet intervention programs in people with MS. Key messages Overall diet quality was not associated with 5-year change in depression, anxiety and fatigue in people with MS. However, some individual food groups were associated with a change in depression and anxiety.

Wearing-off symptoms during standard and extended natalizumab dosing intervals: Experiences from the COVID-19 pandemic

Natalizumab effectively prevents disease activity in relapsing-remitting multiple sclerosis, but many treated patients report subjective wearing-off symptoms at the end of the 4-week interval between infusions. Extended interval dosing (EID) is a promising strategy to mitigate the risk of natalizumab-associated progressive multifocal leukoencephalopathy, but it is unknown whether EID affects wearing-off symptoms. In this observational study, we evaluated if prevalence or intensity of wearing-off symptoms changed when natalizumab dosing intervals were extended from 4 to 6 weeks in 30 treated patients during the outbreak of COVID-19 in Norway. New or increased wearing-off symptoms during EID were reported by 50%. Symptom increase was more frequent among patients with pre-existing wearing-off symptoms during standard dosing compared to patients without such pre-existing symptoms [p = 0.0005]. Our observations support the need to study the effect of EID on wearing-off symptoms in randomized controlled trials.