Background

Serum neurofilament light chain (sNfL) reflects neuro-axonal damage and may qualify as a biomarker of suboptimal response to disease modifying therapy (DMT).

Objectives

To investigate the predictive value of sNfL in clinically isolated syndrome (CIS) and relapsing-remitting (RR) MS patients with established DMT for future MS disease activity in the Swiss MS Cohort Study.

Methods

All patients were on DMT for at least 3 months. sNfL was measured 6 or 12-monthly with the NF-light^®assay. The association between sNfL and age was modeled using a generalized additive model for location scale and shape. Z-scores (sNfLz) were derived thereof, reflecting the deviation of a patient sNfL value from the mean value of same age healthy controls (n=8865 samples). We used univariable mixed logistic regression models to investigate the association between sNfLz and the occurrence of clinical events (relapses, EDSS worsening [≥1.5 steps if EDSS 0; ≥1.0 if 1.0-5.5 or ≥0.5 if >5.5] in the following year in all patients, and in those fulfilling NEDA-3 criteria (no relapses, EDSS worsening, contrast enhancing or new/enlarging T2 lesions in brain MRI, based on previous year). We combined sNfLz with clinical and MRI measures of MS disease activity in the previous year (EDA-3) in a multivariable mixed logistic regression model for predicting clinical events in the following year.

Results

sNfL was measured in 1062 patients with 5192 longitudinal samples (median age 39.7 yrs; EDSS 2.0; 4.1% CIS, 95.9% RRMS; median follow-up 5 yrs). sNfLz predicted clinical events in the following year (OR 1.21 [95%CI 1.11-1.36], p<0.001, n=4624). This effect increased in magnitude with increasing sNfLz (sNfLz >1: OR 1.41 [95%CI 1.15-1.73], p=0.001; >1.5: OR 1.80 [95%CI 1.43-2.28], p<0.001; >2: OR 2.33 [95%CI 1.74-3.14], p<0.001). Similar results were found for the prediction of future new/enlarging T2 lesions and brain volume loss. In the multivariable model, new/enlarging T2 lesions (OR 1.88 [95%CI 1.13-3.12], p=0.016) and sNfLz>1.5 (OR 2.18 [95%CI 1.21-3.90], p=0.009) predicted future clinical events (n=853), while previous EDSS worsening, previous relapses and current contrast enhancement did not. In NEDA-3 patients, change of sNfLz (per standard deviation) was associated with a 37% increased risk of clinical events in the subsequent year (OR 1.37 [95%CI 1.04-1.78], p=0.025, n=587).

Conclusions

Our data support the value of sNfL levels, beyond the NEDA3 concept, for treatment monitoring in MS clinical practice.

Background

Restrictions imposed by the National and local authorities to mitigate the spread of Coronavirus disease-19 (COVID-19) posed unique challenges in the access to care and management of people with multiple sclerosis (PwMS).

Objectives

To collect data about the impact of the COVID-19 emergency on access to care for PwMS and analyze influence on treatment practices of MS neurologists worldwide.

Methods

Between March and July 2020 the European Committee for Treatment and Research in MS (ECTRIMS) promoted an online survey among Council members and MS specialists worldwide, covering five major areas: general information; MS patient access to care; management of relapses and visits; use of disease modifying therapy (DMT); experience with COVID-19 MS patients.

Results

Three-hundred-sixty neurologists (46% females, median age 48 years) from 52 countries (Europe 68%; Central/South America 17%; North America 10%, others 5%) completed the survey. Seventy-five percent worked within a specialized MS centre, 42% followed > 1000 patients. Ninety-eight percent of respondents reported COVID-19 pandemic had a negative impact on patients’ care. Routine MS clinical activities were suspended in 63% of cases and only urgent visits were guaranteed. Telemedicine services (mainly calls, video-calls, messaging) were provided by 90% of respondents: only in 20% of cases telemedicine was already in use in the practice. Forty-five percent revealed changes in relapse treatment: dosage and/or duration reduction 30%; treatment offered only for severe relapses 36%; treatment delivered at home 28%. As for DMT, 98% of respondents felt no modification was needed for interferons and glatiramer; 48-60% deemed no change was needed for dimethyl fumarate, teriflunomide, fingolimod and siponimod, while nearly 25% considered switching/suspending these agents based on lymphopenia. On the other hand, for natalizumab 31% applied an extended-dose regimen, for cladribine and alemtuzumab 42-52% considered postponing treatment in any case as the best choice. For anti-CD20 monoclonal antibodies, postponing treatment in any case (32%) or based on the patient immunophenotype (25%) were the preferred options. Sixty-one percent of respondents had at least one patient affected by COVID-19, 27% had at least one patient with severe infection; 70% of severe cases were on DMT. Finally, 11% of respondents reported at least one COVID-19 related death and 36% of fatal cases were on DMT.

Conclusions

While analysis of geographic differences is ongoing, the survey highlighted that COVID-19 pandemic is having a major impact on MS care worldwide. Telemedicine has a great potential to mitigate issues and needs to be potentiated/implemented de novo at most centres. As for DMT, major changes regarded cladribine, alemtuzumab and anti-CD20. Collecting standardized, reliable data on the potential impact of DMT on COVID-19 in PwMS is urgently needed to inform appropriate treatment decisions.

Background

Additional biomarkers reflecting disease activity and predicting severity of multiple sclerosis (MS) are urgently needed.

Objectives

To explore whether intrathecal immunoglobulin (Ig) M synthesis is associated with time from disease onset to first relapse, MS Severity Score (MSSS) and time to first initiation of high efficacy disease modifying treatments (DMT) in patients with relapsing MS in the Swiss Multiple Sclerosis Cohort study.

Methods

487patients were categorized by presence of CSF oligoclonal IgG bands (OCGB) and quantitative intrathecal IgG and IgM production (Intrathecal Fraction, IF). Treatments were classified according to "no therapy", "platform", "oral" and "high efficacy". Multivariable Cox proportional hazard models or a multivariable linear model, adjusted for relevant covariables, were used to assess time from disease onset to described endpoints and associations with the MSSS.

Results

OCGB were present in 89.3%, IgGIF in 66.3%, IgMIF in 26.9% and IgAIF in 11.9% of patients. Patients with IgMIF had a shorter interval from disease onset to first relapse (HR 1.887 [CI 1.181, 3.014], p<0.01) compared to those without OCGB and IgGIF and IgMIF. Quantitatively, patients with IgMIF above versus below the median had a 1.75- fold increased hazard of occurrence of a first relapse (HR 1.746 [CI 1.097, 2.781]; p=0.019). IgMIF positive patients had on average a 1.24 steps higher MSSS compared with those without any intrathecal Ig synthesis (estimate: 1.243 [CI 0.501,1.986], p<0.01), followed by patients with OCGB and quantitative production of IgGIF (estimate: 0.966 [CI 0.283, 1.650], p<0.01) and patients with only OCGB (estimate: 0.716 [CI -0.030, 1.461], p=0.060). Accordingly, patients with IgMIF production had a shorter interval to initiation of high efficacy DMT (HR 2.788 [CI 1.306, 5.951], p<0.01). Quantitatively, above versus below median IgMIF was associated with a 2.36-fold risk of escalation to a high efficacy DMT (HR 2.361 [CI 1.304, 4.277]; p<0.01).

Conclusions

In relapsing MS, presence of intrathecally produced IgM is associated with higher disease activity, more severe disease course and earlier use of high efficacy treatments. Intrathecally produced IgM may qualify as useful prognostic biomarker for therapeutic decision making in early stage of disease.

Background

Intrathecal IgM synthesis was reported to be associated with higher clinical disease activity and severity. We found an association also with earlier use of high efficacy treatments in relapsing MS (RMS).

Objectives

To explore whether patients with intrathecal IgM synthesis show a) higher serum neurofilament light chain levels (sNfL) as a reflection of neuronal damage, or b) signs of increased disease severity in cerebral MRI, in patients with RMS followed in the Swiss MS Cohort Study.

Methods

487 patients were categorized by presence of oligoclonal IgG bands (OCGB) and intrathecally produced IgG/M:

1) OCGB-/IgG-/IgM- (reference [ref]);

2) OCGB+/IgG-/IgM-;

3) OCGB+/IgG+/IgM- and

4) OCGB+/IgG+/IgM+.

sNfL was measured (at baseline and every 6- or 12 months) with the NF-light^® assay. Age-dependent sNfL z-scores (sNfLz) were modelled in 8865 healthy control samples to reflect the deviation of a patient sNfL value compared to mean values observed in same age healthy controls. Yearly T2 lesion number and occurrence of new/enlarging T2 lesions were automatically assessed in cerebral MRIs and checked manually. Contrast enhancing lesions (CEL) were manually quantified. Linear or negative binomial mixed models were used to investigate the associations between the four CSF Ig patterns and longitudinal sNfLz and MRI measures, adjusted for DMT and other covariates.

Results

IgM+ patients had higher sNfLz vs reference (estimate 0.50 [CI 0.12, 0.89], p=0.011), whereas those with only OCGB+ (0.11 [-0.28, 0.50], p=0.582) or with OCGB+/IgG+ (0.20 [-0.16, 0.56], p=0.270) did not (n=2970 observations). This was confirmed when analyzing only untreated patients adjusting for T2 and CEL numbers (1.16 [0.47, 1.86], p<0.01 vs 0.58 [-0.11, 1.27], p=0.1022 vs 0.51 [-0.11, 1.13], p=0.108 vs ref, respectively) (n=234).

IgM+ patients had 2.28-fold more T2 lesions ([1.51, 3.44], p<0.01) vs ref; for patients with only OCGB+ (1.61 [1.07, 2.43], p=0.0237) or OCGB+/IgG+ (1.58 [CI 1.08, 2.32], p=0.0179) (n=1580) this association was weaker.

IgM+ was associated with a 2.47-fold risk for new/enlarging T2 lesions on yearly follow-up MRIs vs ref (2.47 [1.28, 4.78], p<0.01) but not the two other patient groups (1.84 [CI 0.93; 3.65], p=0.0799 and 1.61 [CI 0.87; 2.95], p=0.1280) (n=861).

Conclusions

Intrathecal IgM synthesis was consistently associated with quantitative measures of neuro-axonal injury and disease severity in RMS. Our findings strongly support the clinical utiliy of this biomarker.

Background

In relapsing MS, blood NfL has emerged as a promising biomarker of disease activity and worsening. The ability of serum NfL (sNfL) to detect relapse-independent disability progression is less well established.

Objectives

We investigated whether patients followed in the Swiss Multiple Sclerosis Cohort (SMSC) without any relapses during follow-up, had higher sNfL levels when experiencing confirmed disability progression independent of relapses (PIRA) as compared to stable patients. Secondly, we explored whether baseline (BL) sNfL could predict PIRA.

Methods

BL and 6- or 12-monthly follow-up sNfL were measured by Simoa NF-light^® assay in 4608 samples from 806 relapse-free MS patients and 8865 serum samples from 4133 healthy controls (median age 45 yrs). Age-dependent sNfL z-scores (sNfLz) were modeled in healthy controls using a generalised additive model for location scale and shape to reflect the deviation of a patient sNfL value from the mean value of same age healthy controls. PIRA was defined as an EDSS increase of ≥1.5 steps if baseline EDSS 0, ≥1.0 if 1.0-5.5, or ≥0.5 if >5.5, confirmed after ≥6 months. We used mixed effects models to investigate the association between PIRA, clinical parameters, disease modifying treatment, and log(sNfL) as dependent variable at each sampling. The predictive value of BL sNfLz was investigated by uni- and multivariable Cox proportional hazards models.

Results

806 (4608 samples) of 1399 patients in the SMSC did not experience relapses during a median follow-up of 4.7 years (57.6%; BL: 715 RRMS, 43 SPMS, 48 PPMS; median age 42 yrs; samples/patient: 5; EDSS 2.0). PIRA occurred in 153/806 (19.0%). In a multivariable model, sNfL was positively associated with age (1.7%/year [95%CI 1.5;2.0], p<0.001) and EDSS at BL (7.6%/step, [5.8;9.6], p<0.001), whereas it was decreased when sampled during monoclonal antibody therapy (-10.8%, [-14.7;-6.6], p<0.001) or oral MS treatments (-10.4%, [-14.1;-6.5%], p<0.001) as compared to untreated timepoints. Importantly, patients experiencing PIRA had 11.6% higher sNfL levels, compared with stable patients (4.5;19.2, p=0.001). The hazard of future PIRA increased by 23.5% (8.3;40.8, p=0.002) per 1 standard deviation higher BL sNfLz. This finding was confirmed after adjusting for age, EDSS score and treatment at BL (27.8%, [11.5;46.5], p<0.001; sNfLz > 2: 2.5-fold risk [95%CI 1.7-3.9], p<0.001 for PIRA event vs. sNfLz < 2).

Conclusions

Our data support the value of sNfL to capture and predict neuro-axonal injury leading to disability progression independent from relapses.

Background

Serum neurofilament light chain (sNfL) levels reflect neuroaxonal damage and relate to disease activity in MS. sNfL may qualify as well as a biomarker of suboptimal treatment response to disease modifying therapies (DMT). Establishment of age-dependent reference ranges in healthy controls is a prerequisite for developing this biomarker for clinical use.

Objectives

To compare on-treatment sNfL levels with values from a healthy control cohort and to investigate the effect of DMTs on sNfL levels in patients from the Swiss MS Cohort Study.

Methods

sNfL was measured (at baseline and every 6- or 12 months) with the NF-light® assay. Age-dependent sNfL z-scores (sNfLz) were modeled in healthy controls using a generalized additive model for location scale and shape to reflect the deviation of a patient sNfL value from the mean value of same age healthy controls. Linear mixed models were used to investigate the associations between clinical characteristics, DMT and longitudinal sNfLz. Interaction terms and splines were used to model sNfLz and for comparison log(NfL), and their dynamics under treatment.

Results

sNfL was measured in 1368 patients with 7550 longitudinal samples (baseline: median age: 41.9 yrs; 5.4% CIS, 83.2% RRMS, 5.6% SPMS, 5.8% PPMS; median EDSS: 2.0; median follow-up: 4.6 yrs) and 4133 healthy controls with 8865 samples (median age: 44.8 yrs). In the multivariable model, sNfLz increased with EDSS (0.131/step, [95% CI 0.101;0.161]), recent (<120 days) relapse (0.739 [0.643;0.835]) decreased with age (-0.014/year [-0.02;-0.009]), and time on DMT (-0.040/year [-0.054;-0.027]); sNfLz were lower when sampled while on more effective DMT (oral versus platform injectables: -0.229 [-0.344;-0.144]; monoclonal antibodies (mAB) versus platform injectables: -0.349 [-0.475;-0.224]), (p<0.001 for all associations). sNfLz were inversely associated with the hierarchy in efficacy of mAB over orals and orals over platform therapies with regard to slope and extent of decrease (interaction between time under DMT and DMT class: p<0.001). sNfLz, but not log(NfL) showed normalization of sNfL levels by mAB to healthy control levels.

Conclusions

The dynamic change of sNfLz on DMT reflects closely their relative clinical efficacy and is more meaningful than log(sNfL) by excluding age as a confounding factor. Use of sNfLz based on a large normative database as an age-independent sNfL measure improves the accuracy of the sNfL signal and hence their clinical utility.

Background

The MAGNIFY-MS study (NCT03364036) aims to determine the onset of action of cladribine tablets 3.5 mg/kg over 2 years (CT3.5) in patients with relapsing multiple sclerosis (RMS). Efficacy data from the pivotal trial CLARITY showed that outcomes in CT3.5-treated patients were superior to placebo with regard to number and relative reduction of standardized combined unique active (CUA) lesions over the 96-week trial. Carrying out early and frequent magnetic resonance imaging (MRI) will provide valuable insights into the onset of action of CT3.5.

Objectives

To report on the onset of action of CT3.5 by observing changes in counts of CUA MRI lesions during the first 6 months of the MAGNIFY-MS study.

Methods

MRI scans were performed at screening, baseline, and at months 1, 2, 3 and 6 following CT3.5 treatment on patients with highly active RMS. Differences in CUA lesions between post-baseline periods (period 1, months 1–6, period 2, months 2–6, and period 3, months 3–6) were compared to the baseline period. CUA lesion count was standardized to period length and number of MRIs in a period. A mixed effects linear model was used to account for within pooled centre correlation and adjusted for CUA lesion count during the baseline period, age, and baseline expanded disability status scale (EDSS; >3, ≤3). Type-I-error inflation due to multiple testing was controlled by a gatekeeping procedure.

Results

The full analysis set considered for primary analysis included 270 patients. Reductions in mean CUA count were observed from month 1 onwards compared to baseline; by -1.193 in period 1, -1.500 in period 2 and -1.692 in period 3 (all p<0.0001). In particular, the mean T1 Gd+ lesion counts were decreased from month 2 onwards compared to baseline; by -0.857 at month 2, -1.355 at month 3 and -1.449 at month 6 (all p<0.0001). Sensitivity analysis using negative binomial distribution showed that the treatment effect increased with time measured as lack of CUA in subsequent periods; by 61% in period 1, 77% in period 2, and 87% in period 3 (all p<0.0001). The proportion of patients without any CUA lesions increased in the first 6 months; by 52% in period 1 (p=0.0241), 66% in period 2 (p<0.001), and 81% in period 3 (p<0.001).

Conclusions

MRI was used to assess disease activity in a group of highly active RMS on CT3.5 treatment from one month onwards. Data show an early onset of action on CUA lesions that was significant from month 1 versus baseline, with a treatment effect that increased over the first 6 months.

Background

The pathogenesis of neurodegeneration in multiple sclerosis (MS) is multifactorial and the determinants of brain atrophy rates are not completely understood.

Objectives

To investigate the association between annualized atrophy rate (AAR) of multiple brain measures (regional cortical thickness (CTh), volumes of basal ganglia, thalamus, white matter, gray matter, brain and brain parenchymal fraction (BPF)) and: (1) annualized rate of new and enlarging white matter lesions (WMLs); (2) annualized rate of resolved WMLs; (3) occurrence of progression independent of relapse activity (PIRA) during follow-up.

Methods

We included 1573 1.5T or 3T brain MRI scans from 378 patients of the Swiss MS Cohort Study (331 relapsing-remitting MS (RRMS), 27 clinically isolated syndrome (CIS), 11 secondary-progressive MS (SPMS), 9 primary-progressive MS (PPMS); 70% female; median age: 41.9 yrs; disease duration: 8.3 yrs; EDSS: 2.0; follow-up time: 4.0 yrs). Longitudinal changes in WMLs were obtained using an automated prototype (LeMan-PV). Brain volumes and CTh AARs were obtained using FreeSurfer longitudinal pipeline (v6.0) after WMLs filling. In patients fulfilling PIRA an EDSS progression had to be confirmed ≥6 months after the index event. Multivariable generalized linear models were used to model the association between AAR (dependent variable) and independent variables (1-3), correcting for age, sex, disease duration and baseline EDSS. p-values were adjusted for Bonferroni multiple comparison correction; for vertex-wise CTh analysis, Monte Carlo Z simulation was performed (cluster threshold p<0.05).

Results

We found positive associations between annualized rate of new and enlarging WMLs and (i) CTh AAR of 8 extensive clusters (bilateral frontal, temporal and occipital regions and right insula, all p<0.01) and (ii) AAR of: caudate bilaterally (p=0.02), white matter volume, brain volume and BPF (p<0.001 for all).

We also found a negative association between annualized rate of resolved WMLs and CTh AAR in 3 cortical clusters (right insula, precentral area and anterior cingulate region, all p<0.05); no associations with AAR of volumes emerged.

57 patients fulfilled PIRA whereas 295 experienced no EDSS progression events: no significant differences in AAR measures were found between these two groups.

Conclusions

In a large cohort of MS patients, with a median follow-up of 4 years, local radiological inflammatory and reparative activity were associated with AAR in multiple brain regions. PIRA did not seem to be related to increased AAR in any of the regions studied.

Background

Gadolinium (Gd)-based contrast agents are widely used to assess disease activity and treatment response by MRI in multiple sclerosis (MS). There is, however, increasing concern about their safety as their repeated administration may lead to brain parenchymal accumulation, while preclinical models suggest that they induce mitochondrial toxicity and neuronal cell death. Moreover, recent reports have demonstrated that three-dimensional (3D) T2-weighted Fluid-Attenuated-Inversion-Recovery (FLAIR) is highly sensitive in detecting new or enlarging MS lesions.

Objectives

To explore whether the presence of contrast enhancing lesions (CEL) based on Gd injection is more sensitive in detecting lesional activity in clinically stable MS patients in comparison to the analysis of new or enlarging MS lesions by 3D FLAIR.

Methods

MS patients being part of the observational, multicenter Swiss Multiple Sclerosis Cohort Study (SMSC) with contrast enhanced T1-weighted (T1w) images were included. Clinical stability was defined as no relapse and no Expanded Disability Status Scale (EDSS) increase during at least twelve months prior to MRI. Presence of CEL was assessed on contrast enhanced T1w images. Presence of new or enlarging T2w lesions was assessed manually on 3D FLAIR in an independent analysis by a different investigator in clinically stable MS patients presenting with CEL.

Results

3930 MRI scans (3.0 Tesla n=1497 (38%)) in 1057 participants (685 women, median age 42.0 years, 941 with relapsing MS, 116 with progressive MS, median EDSS 2.0 (range 1.5-3.5), median disease duration 7.4 years) were included.

Of 2620 MRI scans (66.7%) acquired in clinically stable conditions 46 (1.8%) demonstrated CEL. In all of these, new or enlarging T2w lesions were detectable by 3D FLAIR when a previous MRI was available for comparison (previous MRI available in 29/46; median number of new or enlarging T2w lesions: 3 (range 1-41, total number 176); median number of CEL: 1 (range 1-4, total number 47)).

Conclusions

In our large cohort from clinical practice, the assessment of new or enlarging lesions by 3D FLAIR was equally sensitive as the quantification of CEL to detect disease activity in clinically stable MS patients, challenging current practice of the use of Gd-enhanced MRI for monitoring of MS in clinical routine.

Background

Neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS) have a different pathophysiology. Accumulating evidence suggests that the choroid plexus plays a pivotal role in the pathogenesis of MS. However, MRI data comparing the choroid plexus volume between MS and NMOSD are scarce.

Objectives

To compare the choroid plexus volume in MS vs. NMOSD in vivo using high-resolution 3D MRI data. Migraine patients and healthy individuals served as control groups.

Methods

We included 95 MS patients [45% secondary progressive (SP); mean age 51.0±11.5 years; disease duration 20.8±10.4 years, 62% female; median Expanded Disability Status Scale (EDSS) 4.0], 43 NMOSD patients [28/43 anti-aquaporin 4 antibody positive; 11/43 anti-myelin oligodendrocyte glycoprotein antibody positive; 87% female; mean age 50.0±13.8 years; disease duration 6.8±7.3 years, median EDSS 3.0], 38 migraine patients [mean age 39±13 years, 79% female; 15/38 migraine with aura] and 65 healthy individuals [HCs, mean age 41±17 years, 48% female]. The choroid plexus of the lateral ventricles and T2-weighted (T2w) white matter lesions (WMLs) were segmented fully automated on T1-weighted (T1w) magnetization-prepared rapid gradient echo (MPRAGE) images and fluid attenuated inversion recovery sequences (FLAIR, voxel size of both sequences 1x1x1 mm³), respectively, using a supervised deep learning algorithm (multi-dimensional gated recurrent units). Total intracranial volume (TIV) and lateral ventricle volumes were assessed fully automated using Freesurfer. All outputs were reviewed and manually corrected (if necessary) using 3D-Slicer by trained raters who were blinded to the clinical information. Group differences were analyzed using multivariable generalized linear models (GLMs) adjusted for age, gender, TIV and lateral ventricle volume. Cohens’ d was used to calculate the standardized difference between the respective groups. Given p-values are adjusted for multiple comparisons (Bonferroni).

Results

Mean choroid plexus was larger in MS compared to NMOSD (1907±455 vs. 1467±408 µl; p<0.001, d=0.86), HCs (1663±424 µl; p=0.007, d=1.17) and migraine (1527±366 µl; p=0.02, d=0.72). There was no statistical difference in the choroid plexus volume between NMOSD, migraine and HCs. The choroid plexus was marginally larger in RRMS than SPMS (1959±482 vs. 1875±476 µl; p=0.28; d=0.17) and in untreated MS patients compared to MS patients on disease modifying therapy (2111±382 vs. 1876±459 µl; p=0.36). However, these differences did not reach statistical significance after correction for multiple comparisons. There was no association between the choroid plexus volume and total T2w WML volume in MS.

Conclusions

Patients with MS have larger choroid plexus than HCs, migraine and NMOSD patients. Further studies are warranted to investigate the respective roles of the choroid plexus in the pathogenesis of MS and NMOSD.

Abstract

Multiple Sclerosis is associated with an increased risk of infections. This increased risk is driven by the disability caused by MS and the disease modifying drugs (DMD) that are used to treat MS.

This teaching course is designed to inform the practitioner about infection risks with multiple sclerosis disease modifying drugs. The content will address the immune dysregulation occasioned by each class of DMTs and the anticipated infections occurring as a consequence, the current state of knowledge with respect to the observed risk of infection with each class of agent, and risk mitigation strategies. Various disease states will be described to improve the practitioner’s ability for early detection. Special attention will be afforded to progressive multifocal leukoencephalopathy, cryptococcal meningitis, and infection risks with B cell depleting agents. Additionally, the effect of DMTs on COVID morbidity and mortality will also be discussed.

The participants will learn about infectious risks associated with different DMDs, how to diagnose them and how to mitigate these infectious risks.

Abstract

Multiple Sclerosis is associated with an increased risk of infections. This increased risk is driven by the disability caused by MS and the disease modifying drugs (DMD) that are used to treat MS.

This teaching course is designed to inform the practitioner about infection risks with multiple sclerosis disease modifying drugs. The content will address the immune dysregulation occasioned by each class of DMTs and the anticipated infections occurring as a consequence, the current state of knowledge with respect to the observed risk of infection with each class of agent, and risk mitigation strategies. Various disease states will be described to improve the practitioner’s ability for early detection. Special attention will be afforded to progressive multifocal leukoencephalopathy, cryptococcal meningitis, and infection risks with B cell depleting agents. Additionally, the effect of DMTs on COVID morbidity and mortality will also be discussed.

The participants will learn about infectious risks associated with different DMDs, how to diagnose them and how to mitigate these infectious risks.

Abstract

Multiple Sclerosis is associated with an increased risk of infections. This increased risk is driven by the disability caused by MS and the disease modifying drugs (DMD) that are used to treat MS.

This teaching course is designed to inform the practitioner about infection risks with multiple sclerosis disease modifying drugs. The content will address the immune dysregulation occasioned by each class of DMTs and the anticipated infections occurring as a consequence, the current state of knowledge with respect to the observed risk of infection with each class of agent, and risk mitigation strategies. Various disease states will be described to improve the practitioner’s ability for early detection. Special attention will be afforded to progressive multifocal leukoencephalopathy, cryptococcal meningitis, and infection risks with B cell depleting agents. Additionally, the effect of DMTs on COVID morbidity and mortality will also be discussed.

The participants will learn about infectious risks associated with different DMDs, how to diagnose them and how to mitigate these infectious risks.