Imperial College London
Department of Brain Sciences

Author Of 4 Presentations

Epidemiology Oral Presentation

PS05.02 - Validation of three Secondary Progressive Multiple Sclerosis classification methods in five registries within the SPMS Research Collaboration Network

Abstract

Background

Assigning Secondary Progressive Multiple Sclerosis (SPMS) course consistently is challenging as it is based on a gradual worsening in neurological disability independent of relapses. Clinical SPMS assignment may therefore vary between registries depending on clinical practice. Consequently, a comparison of SPMS between registries would benefit from an objective definition of SPMS.

Objectives

To validate three different methods for classifying patients into Relapsing Remitting Multiple Sclerosis (RRMS) or SPMS, compared to the clinical assignment, in five European Multiple Sclerosis (MS) registries.

Methods

Data from MS registries in Czech Republic (11,336 patients), Denmark (10,255 patients), Germany (23,185 patients), Sweden (11,247 patients), and the United Kingdom (UK) (5,086 patients) were used. Patients with either RRMS or SPMS, age ≥ 18 years at index date (date with the latest Expanded Disability Status Scale (EDSS) observation) were included. Index period was 01/2017 - 12/2019. Three EDSS centric classification methods were applied; method 1: a modified real world EXPAND criteria (Kappos, L. et al., 2018. The Lancet 391(10127), 2018), method 2: the data-derived definition from Melbourne University but without pyramidal Functional Score (Lorscheider, J. et al., 2016. Brain 139(9)), method 3: the decision tree classifier from Karolinska Institutet (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674). The classifications were compared to the clinical assignment, where sensitivity (SPMS as true positive), specificity (RRMS as true negative) and accuracy were calculated as similarity measurements.

Results

The overall classification performance (sensitivity, specificity, accuracy) among classifiable patients were; method 1: (0.47, 0.85, 0.79), method 2: (0.77, 0.87, 0.85), method 3: (0.84, 0.83, 0.84). The proportions of unclassifiable patients with each method were; method 1: 20.0%, method 2: 32.2%, method 3: 0%. Methods 2 & 3 provided a high sensitivity, specificity and accuracy, while method 1 provided high specificity but low sensitivity. Method 3 was the only method having no unclassifiable patients.

Conclusions

Our findings suggest that these methods can be used to objectively assign SPMS with a fairly high performance in different registries. The method of choice depends on the research question and to what degree unclassifiable patients are tolerable.

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Observational Studies Oral Presentation

PS05.04 - Ongoing disease modifying treatment associated with mis-classification of secondary progressive as relapsing-remitting multiple sclerosis

Abstract

Background

Until recently, disease modifying treatment options for MS patients with a secondary progressive course (SPMS) were limited, leading to the common practice of off-label treatment with drugs approved for relapsing-remitting MS. We previously showed that applying objective algorithms tend to increase the proportion of SPMS in MS registries, suggesting that SPMS is under-diagnosed in clinical practice, possibly related to available treatment options.

Objectives

To compare characteristics of patients clinically assigned an RRMS course that are re-classified when an algorithm-based SPMS assignment method is applied.

Methods

Data from MS registries in the Czech Republic (11,336 patients), Denmark (10,255 patients), Germany (23,185 patients), Sweden (11,247 patients) and the United Kingdom (5,086 patients) were used. Inclusion criteria were patients with relapsing remitting (RR)MS or SPMS with age ≥ 18 years at the beginning of the study period (1 January 2017 – 31 December 2019). In addition to clinically assigned SPMS a data-driven assignment method was applied in the form of a decision tree classifier based on age and last EDSS (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674).

Results

Across the five registries 8,372 RRMS patients were re-assigned as SPMS (Denmark: n=1,566, Czech Republic: n=1,958, Germany: n=2,906, Sweden: n=648, United Kingdom: n=1,294) increasing the overall SPMS proportion from 17% to 31%. Re-assigned patients tended be younger, were older at onset and had experienced a quicker progression to SPMS. The overall proportion of clinically assigned SPMS patients on disease modifying treatments (DMTs) was 36% but varied greatly between registries (Czech Republic: 18%, Denmark: 35%, Germany: 50%, Sweden: 40%, and the United Kingdom: 12%) whereas a higher proportion of 69% (OR=4.0, P<0.00004) were on DMTs among RRMS patients re-assigned as SPMS (Czech Republic: 71%, Denmark: 68%, Germany: 78%, Sweden: 80%, and the United Kingdom 40%).

Conclusions

SPMS patients on DMTs may be clinically mis-classified as RRMS, most likely by not being re-assigned to SPMS after conversion has occurred. This challenges the use of time to SPMS conversion as an outcome in comparative effectiveness studies using real world evidence data and argues for the use of objective classification tools in the analysis of MS patient populations.

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COVID-19 Late Breaking Abstracts

SS02.01 - COVID-19 in people with MS: A large community-based study of the UK MS Register

Speakers
Presentation Number
SS02.01
Presentation Topic
COVID-19
Lecture Time
10:45 - 10:57

Abstract

Background

The Coronavirus Disease 2019 (COVID-19) pandemic has introduced uncertainties into the multiple sclerosis (MS) community and the focus so far has been the severity of infection among people with MS (pwMS) who have COVID-19. This approach has left questions about the risk of contracting disease in pwMS unanswered which has implications as society gradually returns to normal.

Objectives

To evaluate the trend of COVID-19 incidence in pwMS, their behaviour in response to the outbreak, and the effect of their demographic and clinical characteristics on the likelihood of contracting COVID-19.

Methods

The United Kingdom MS Register (UKMSR) has been collecting demographic and MS related data since 2011 from pwMS all over the UK. On 17 March 2020, existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this on-going study, pwMS answer a COVID-19 related survey at participation and a different follow-up survey every two weeks depending on whether they report COVID-19.

Results

We estimate the nationwide overall incidence of COVID-19 in pwMS as 10% (n=522) among 5237 participants until 24 June 2020. The weekly incidence peaked during the 2nd week after lockdown started on 23 March 2020 (13.2%) and remained high until it dropped to 3.5% in the 10th week. The mean (standard deviation) age of the study population was 52.4 (11.9), 76.1% (n=3985) were female, and 95.7% (n=5012) were of white ethnicity. PwMS with a higher web-based Expanded Disability Status Scale (EDSS) score are more likely to self-isolate (odds ratio [OR] 1.389, 95%CI [confidence interval] 1.333−1.447). PwMS who are taking disease modifying therapies (DMTs) and those with progressive MS tend to self-isolate more (OR 1.259, 95%CI 1.059−1.497 and OR 1.245, 95% CI 1.013−1.531, respectively). Older age, progressive MS, and white ethnicity were associated with a lower likelihood of having COVID-19 (OR 0.969, 95%CI 0.957−0.982 and OR 0.595, 95% 0.422−0.838 and OR 0.495, 95%CI 0.347−0.705, respectively). Gender, EDSS, MS Impact Scale version 29 scores and DMTs did not alter the likelihood of contracting COVID-19.

Conclusions

To our knowledge, this is the largest community-based study of COVID-19 in pwMS worldwide. The trend of COVID-19 in pwMS is comparable to that of the UK general population. During a period with strict physical distancing measures, pwMS are not at an increased risk of contracting COVID-19.

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COVID-19 Late Breaking Abstracts

SS02.04 - First results of the COVID-19 in MS Global Data Sharing Initiative suggest anti-CD20 DMTs are associated with worse COVID-19 outcomes

Abstract

Background

As the COVID-19 pandemic amplifies, efforts to minimise the risk on vulnerable people are essential. People with multiple sclerosis (MS) may be a vulnerable group due to the high proportion taking long-term immunosuppressive disease-modifying therapies (DMTs). Studies from Italy and France suggest older age, higher disability and progressive MS are associated with severe COVID-19, yet there remains uncertainty around the influence of DMTs.

Objectives

Given the many approved MS DMTs and the relatively low frequency of COVID-19 in MS patients per country, international data sharing is desirable to examine the impact of DMTs on COVID-19 severity. Here, we present the first results of the COVID-19 in MS global data sharing initiative of the MS International Federation and MS Data Alliance and many other data partners to inform MS clinical management during the COVID-19 pandemic.

Methods

Clinician-reported data from 21 countries were aggregated into a dataset of 1540 patients. Characteristics of admission to hospital, admission to intensive care unit (ICU), need for artificial ventilation, and death, were assessed in patients with confirmed or suspected COVID-19 infection using log-binomial regression. Adjusted prevalence ratios (aPR) were calculated adjusting for age, sex, MS type, and Expanded Disability Status Scale (EDSS).

Results

Of 1540 patients, 476 (30.9%) with suspected and 776 (50.4%) with confirmed COVID-19 were included in the analysis. Older age, progressive MS and higher EDSS were associated with higher frequencies of severe outcomes. Anti-CD20 DMTs, ocrelizumab and rituximab, were positively associated with hospital admission (aPRs=1.19 & 1.58), ICU admission (aPRs=3.53 & 4.12), and the need for artificial ventilation (aPRs=3.17 & 7.27) compared to dimethyl fumarate. Higher frequencies of all three outcomes were associated with combined anti-CD20 DMT use compared to all other DMTs (hospitalisation aPR=1.49; ICU aPR=2.55; ventilation aPR=3.05) and compared to natalizumab (hospitalisation aPR=1.99; ICU aPR=2.39; ventilation aPR=2.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases and upon exclusion of each contributing data source in turn. No associations were observed between DMTs and death.

Conclusions

This study used the largest federated international cohort of people with MS and COVID19 currently available. We demonstrate a consistent association of anti-CD20 DMTs with hospitalisation, ICU admission and use of artificial ventilation suggesting their use among MS patients at risk for COVID-19 exposure may be a risk factor for more severe COVID-19 disease. To address study limitations, further research incorporating comorbidities, smoking and body mass index is required. Alternative study designs are needed to address questions on COVID-19 susceptibility among people with MS.

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Author Of 12 Presentations

Epidemiology Poster Presentation

LB1155 - Vitamin D levels in the UK MS population and COVID-19 susceptibility (ID 1116)

Abstract

Background

Despite the well-described association between vitamin D and MS, little is known about current behaviours surrounding vitamin D and the corresponding vitamin D status in this group at a population level across the UK. During the COVID-19 pandemic, interest in the role that vitamin D might play in reducing susceptibility to and severity of COVID-19 has come to the foreground.

Objectives

To determine the vitamin D status of the UK MS population, understand the factors that influence it, and examine how vitamin D supplementation affects the risk of COVID-19.

Methods

A cohort study using the UK MS Register was performed. Self-reported data surrounding vitamin D and remotely collected biological samples were collected. 1768 people with MS (pwMS) completed a questionnaire regarding vitamin D-influencing behaviours; dried blood spots were collected from 388 of these pwMS and 309 matched controls, and serum 25(OH)D was measured. Subsequently, 592 participants from this MS cohort prospectively completed questionnaires evaluating symptoms suggestive of COVID-19.

Results

Marked differences were observed between supplementation behaviours with pwMS more likely to take supplements (72% vs 26% controls, p<0.001), and at higher doses (median 1600 IU/day vs 600 IU/day in controls, p<0.001). Serum levels of 25(OH)D were higher in pwMS than controls (71nmol/L, IQR 48 vs 49nmol/L, IQR 27, p<0.001). People with MS who did not supplement had lower serum 25(OH)D levels than non-supplementing controls (median 38 nmol/L, IQR 35 vs 44 nmol/L, IQR 21, p<0.001). 71% of those self-diagnosed with COVID-19 reported taking vitamin D vs 72% without COVID-19. Median dose for those with COVID-19 was reported as 1000 IU/day vs 2000 IU/day in those without (p=0.682).

Conclusions

pwMS living in the UK are more likely to have adequate levels of vitamin D than controls, and is driven by the higher rate and dose of supplementation across this population. This has implications on the design and interpretation of any future clinical trials with vitamin D in this population. In addition, we found no evidence that vitamin D supplementation had an impact on susceptibility to COVID-19 in this population.

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Disease Modifying Therapies – Risk Management Poster Presentation

LB1167 - Reported Covid19 symptoms in patients on oral Disease Modifying Treatmentss (DMTs) at a single centre (ID 1493)

Presentation Number
LB1167
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There is concern amongst the MS community regarding increased risk of COVID-19 infection in patients on Disease Modifying Therapies (DMTs). Guidance from the Association of British Neurologists (ABN) recommends to continue most oral DMTs during the pandemic.

Objectives

To identify number of patients on oral DMTs in a single centre who reported COVID-19 symptoms. To identify how this compares to national infection rate, whether there was a link to lymphocyte counts prior to infection and how many patients stopped or interrupted treatment.

Methods

Patients on oral DMTs (dimethyl fumarate (DMF), teriflunomide (TF) & fingolimod (FING)) were identified through a local database. The pharmacy team called these patients to advise on DMT monitoringduring the pandemic. Patients were also asked if they had experienced any symptoms of COVID-19 infection, had been tested, or had stopped treatment . Recent lymphocyte counts were obtained.

Results

501 patients on oral DMTs were identified (14 on TF, 169 on FING, 318 on DMF). 50% of these were contacted. (DMF=174, FING=71, TF=10). The average age of those on treatment was 45, average EDSS 2.2, and average time on DMT 3.7 years. Of those asked 90% (229) reported that they had not exprienced COVID-19 symptoms. 10% (26) reported that they had experienced COVID-19 symptoms (3 on TF, 8 on FING, 15 on DMF). According to a recent study by the UK Office of National statistics, of those individuals providing blood samples in the UK, 7% tested positive for antibodies to COVID-19. Of those who reported symptoms the last recorded lymphocyte counts were all within accepted ranges, with a mean of 1.2 (TF 2.0, DMF 1.5, FING 0.4). One patient taking DMF died due to COVID-19. Further data will be presented on the average lymphocyte counts in those who did not report symptoms, number of patients who went on to be tested for COVID-19 and the number who stopped or interrupted treatment.

Conclusions

Results present real world data on COVID-19 infection in patients on oral DMTs for MS and how these relate to lymphocyte count and infections rates in general population.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

LB1176 - Anxiety affects the general well-being of people with MS during the COVID-19 pandemic more than the infection itself (ID 1893)

Speakers
Presentation Number
LB1176
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Anxiety and depression are more common in people with multiple sclerosis (pwMS) compared to people without MS. The unpredictable nature of the COVID-19 pandemic has caused widespread distress, but it is unknown if it would affect pwMS disproportionately.

Objectives

To evaluate the impact of the COVID-19 pandemic on the mood and well-being of pwMS in the UK and compare it to that of controls.

Methods

The UK MS Register has been collecting Hospital Anxiety and Depression Scale (HADS) data of pwMS since 2011. In the mood and well-being UKMSR COVID-19 study, we asked pwMS (n=5240) and controls (n=376) to answer questions on General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) for depression and Revised Impact of Event Scale (IES-R) for post-traumatic stress disorder (PTSD) in addition to changes in their lifestyle and well-being during the COVID-19 outbreak.

Results

The HADS score of pwMS (n=2225) during the COVID-19 outbreak had not changed compared to the year before (mean difference 0.004, 95%CI -0.11−0.12, p=0.952 for anxiety and mean difference 0.05, 95%CI -0.05−0.15, p=0.283 for depression). The rate of anxiety (GAD-7>5) in male pwMS (37.2%) was more than controls (24.3%) (p=0.032) but was similar in female pwMS and controls. More male pwMS had moderate to severe depression (PHQ-9>9) compared to controls (28.5.4% vs 12.2%, p=0.003), but again, the rate was similar in females. More pwMS who had COVID-19, experienced anxiety or PTSD (IES-R>32) compared to those without the infection (54% vs 44%, p=0.018; 30.5% vs 22.5%, p=0.024, respectively). The rate of depression was similar in pwMS with or without symptoms of the disease. Anxiety, compared to the actual infection, was more strongly associated with subjective worsening of general health (57.1% vs 37.3%, with anxiety or COVID-19 respectively, p=0.008) or MS symptoms (61% vs 31.3%, p<0.001).

A high proportion of both pwMS and controls did not experience any change in the quality of their relationships. However, more pwMS reported worsening of their relationships compared to controls (21.4% vs 16.7%, p<0.001). The change in loneliness was similar between the two groups with 4 in 10 pwMS and controls feeling lonelier during the outbreak.

Conclusions

Anxiety during the COVID-19 pandemic is having a more profound effect on the general well-being of most patients compared to the infection itself.

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Biostatistical Methods Poster Presentation

P0009 - ENTIMOS: a discrete event simulation model for maximizing efficiency of infusion suites in centres treating multiple sclerosis patients (ID 1630)

Speakers
Presentation Number
P0009
Presentation Topic
Biostatistical Methods

Abstract

Background

Multiple sclerosis patients are treated with intravenous (IV) disease modifying treatments (DMTs). Infusion suite resources are thus vital components of MS patient care. Infusion suites may be dedicated to MS patients, or shared with patients with other neurological conditions, or other patients requiring infusion. Here, we describe a resource utilization model for the infusion suites of Charing Cross (UK), which serves patients with different neurological conditions.

Objectives

To maximize the clinical efficiency of the infusion suite based on three resource constraints: percentage of patients IV MS DMTs, number of infusion chairs, and number of nurses. Efficiency gains in the infusion suite may benefit both patients and the healthcare system.

Methods

ENTIMOS, a discrete event simulation (DES) model, was created using SIMUL8 based on qualitative information from infusion centers and populated with data specific to the Charing Cross hospital neurology infusion suite. Posology, administration information, and rates of immune related-reactions (IRRs) were applied from published data sources from both MS and non-MS DMTs of interest.

The infusion suite model assumes 75 MS and 21 non-MS patients weekly, including up to seven MS patients initiating IV treatment; is equipped with 12 infusion chairs and six beds; and is staffed with a total of six nurses. We simulated the effects of changing the three resource constraints described on the number of patients waiting for an appointment (queue size), the time for patients to get an appointment for their first or subsequent IV treatments (waiting times), and general resource utilization.

Results

Changing the number of chairs, moving a subset of patients from IV to any non-IV alternative treatments, moving patients between MS IV treatments, or changing the allocation of nurse resources may all have an impact on the queue size and waiting times. Once the changes are implemented in the model, existing resources optimised and the queue size reduced, the effective centre throughput can be increased.

Conclusions

ENTIMOS allows users to optimize their use of constrained resources in an infusion suite to improve patient experience and infusion suite efficiency.

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Clinical Outcome Measures Poster Presentation

P0141 - Real-world data on the use of Ocrelizumab, among MS patients: B-cell suppression and clinical outcomes. (ID 934)

Speakers
Presentation Number
P0141
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Ocrelizumab (OCR) is an anti-CD20 B-cell-depleting agent, recently approved for treating relapsing-remitting (RR) MS.

Objectives

In a real-world population of RRMS patients, we described baseline characteristics and clinical outcomes in correlation with the level of OCR-induced B-cell suppression.

Methods

Data were retrospectively collected from 170 RRMS patients, who received 6-monthly 600mg OCR infusions at Imperial College Healthcare NHS Trust from August 2018 to March 2020. Disability progression was defined as ≥1.0 or ≥0.5 Expanded Disability Status Scale (EDSS) increase from baseline EDSS of ≤5.5 or ≥6 respectively. Patients were grouped by level of B-cell depletion after 6 months from the first OCR infusion relative to their baseline B-cell count, into categories of “depleted” (>90%) and “not depleted” (≤90%).

Results

The whole cohort (females 67%, males 33%) was followed up for 5.6 mean months (0-15 months) from OCR initiation. At baseline, the mean age was 45.5 years, the mean disease duration was 13.1 years and the mean EDSS was 4.3. While 15% of patients were treatment naïve, most patients (85%) were escalated to OCR from other disease-modifying therapies: Dimethyl Fumarate (30%), Fingolimod (16%), Alemtuzumab (15%) and Natalizumab (10%). Majority received at least 2 OCR infusions (36%, 51% and 13% with 1, 2 and 3 infusions respectively). The mean B-cell count at baseline was 272/mm3; after OCR initiation, 89% were “depleted” and 11% were “not depleted”. During the follow-up, 7% (n = 12) experienced a relapse and 20% (n = 27) showed disability progression at 4.8 and 6.5 mean months after OCR initiation, respectively. Those who relapsed had in larger proportion new MRI lesions 1 year before OCR initiation (58% vs 20%; p = 0.039) and those experiencing disability progression had longer disease duration (16.8 vs 12.1 mean years; p = 0.039). Although not statistically significant, compared to “depleted” patients, the group without adequate B-cell depletion had a worse clinical outcome, with a larger proportion experiencing a relapse (14% vs 7%; 4.5 vs 4.8 mean months to relapse; p = 0.297).

Conclusions

This study characterizes the use of OCR in a real-world population of RRMS patients. Data suggests that the level of B-cell suppression could be a potential marker of treatment response. This should be validated in further studies with longer follow-up.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0318 - Early monitoring of B cells on ocrelizumab may help to identify those at risk of adverse effects (ID 923)

Presentation Number
P0318
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody used in the treatment of MS. The drug targets CD20 and acts to reduce circulating B cells. Infection is a known adverse effect of treatment. It is not a requirement of the licence to monitor the effect of OCR on B cells counts and the relationship between B cell count and adverse effects is unknown.

Objectives

We aimed to assess the impact of OCR infusions on B cell counts in our patient group and whether there is a relationship between B cell count & adverse events such as infusion reactions or infections

Methods

Lymphocyte subsets were measured for each patient at baseline and before each subsequent infusion. Patients who had received OCR were identified from hospital records & lymphocyte subset results obtained from pathology reports. Date of infusions were noted and B cell data was correlated to determine average counts before or after each dose. Patient records were examined retrospectively to identify reports of adverse events including infection. These were then related to the degree of B cell suppression.

Results

170 people with MS (pwMS) received infusions of ocrelizumab from Sept 2018 to March 2020. Baseline B cell subsets were collected on 145 of these. The mean count ±SD was 279mm3 ±175 (range 44-1290) . Sampling was performed on average 92±62 days prior to dosing. 136 individual pwMS had sampling performed after the first infusion (194 samples in total). In 101 pwMS, between the first and second infusion, the mean B cell counts were 15mm3 ±32.6 . Samples were performed 171±40 days after the first infusion. In 32 pwMS sampled between second and third infusions, mean cell B counts were 13.9mm3 ±29.6 . Samples were performed 353±63 days after the 2nd infusion. In the naïve subgroup (n=10 vs n=71 not naive) there was a more significant drop in B cells 7.7 vs 18.6 (p=0.038) with treatment. However they did not experience more adverse effects. Adverse effects were seen in 54/83 subjects. 21/54 had infusion related reactions. 43 reported infections including herpes (1), cellulitis (1), gastroenteritis (6), upper (18) or lower respiratory tract (7), urinary tract infections (22) or other infection (8). In those who had adverse effects there was no difference in the B cell counts at baseline. However, those who developed infections had a significant reduction in B cells (infection 6mm3 vs no adverse effects 28mm3, p=0.045). This difference persisted after the second dose (infection 5mm3 vs no adverse effects 27mm3, p=0.19). There was however no difference in the absolute lymphocyte counts (p=0.8) , CD8 or NK cells.

Conclusions

This data suggests that regular monitoring of B cell counts, rather than absolute lymphocyte counts, may be a method of identifying those patients at risk of adverse effects, such as infection, following ocrelizumab.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0362 - Novel treatment approach for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing remitting multiple sclerosis (ID 967)

Speakers
Presentation Number
P0362
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Progressive multifocal leukencephalopathy (PML) due to the polyoma JC virus (JCV), remains an untreatable viral infection. Aside from addressing the underlying cause of immunodeficiency, there remains no evidenced-based treatment for PML. PML is rarely seen in fingolimod-treated relapsing remitting multiple sclerosis (RRMS) patients.

Objectives

We present a 62 year-old man with RRMS of 20-years duration treated with fingolimod for 6 years who developed PML and discuss the response to a PD-1 inhibitor, pembrolizumab.

Methods

Onset of illness was insidious with progressive left leg weakness, gait unsteadiness, slurred speech, double vision, asymmetric cerebellar ataxia, bilateral internuclear ophthalmoplegia and spastic paraparesis. Expanded disability status scale (EDSS) increased from 6.0 to 6.5. Fingolimod was immediately withheld.

Results

Magnetic resonance imaging (MRI) scan demonstrated new, patchy, non-enhancing hyperintense lesions within the white matter of frontal lobes, right thalamus and brainstem. 160 copies/ml of JCV-DNA were detected in the cerebrospinal fluid (CSF). Mirtazepine dose was increased to 45mg daily. Despite a few weeks’ clinical stability, MRI appearances and JCV-DNA copies worsened over the next 3 weeks followed by gait deterioration. Maraviroc 300mg twice daily was then introduced. Subtle punctate contrast enhancement, suggestive of a mild immune reconstitution inflammatory syndrome (IRIS), was transiently seen within the midbrain and right frontal areas of signal change 6 weeks after fingolimod cessation, followed by a single focal-to-generalised tonic clonic seizure. EDSS increased to 8.0. Mefloquine 250mg weekly and 3 monthly doses of 200mg pembrolizumab, were administered. Serial CSF examinations and several imaging modalities including spectroscopy and fused FDG-PET-MRI were used to distinguish between PML, PML-IRIS and MS activity. The patient’s symptoms and “PML lesions” on brain MRI scans remained stable, although a handful of small, enhancing ovoid lesions developed between the first two doses of pembrolizumab. Following the second dose of pembrolizumab, a sustained but gradual improvement in imaging and examination parameters was observed with JCV-DNA becoming undetectable 16 weeks following fingolimod withdrawal. EDSS improved from 8.0 to 6.5.

Conclusions

This case highlights several challenges of managing PML, a highly life threatening condition. To our knowledge this is the first case of combined therapy and use of pembrolizumab in a fingolimod-associated PML.

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Epidemiology Poster Presentation

P0482 - Objective classification methods result in an increased proportion of secondary progressive multiple sclerosis in five patient registries (ID 1120)

Abstract

Background

Secondary progressive MS (SPMS) is a research area that is attracting more attention as better treatment options are still needed for this patient group. The assignment of SPMS by clinicians can differ between countries and may be influenced by drug prescription guidelines, reimbursement issues and other societal limitations.

Objectives

To compare the clinically assigned SPMS proportion to three objective SPMS classification methods in five MS registries.

Methods

Data from MS registries in the Czech Republic (CR) (11,336 patients), Denmark (10,255 patients), Germany (23,185 patients), Sweden (11,247 patients) and the United Kingdom (UK) (5,086 patients) were used. Inclusion criteria were patients with relapsing remitting (RR)MS or SPMS with age ≥ 18 years at the beginning of the index period (1 January 2017 – 31 December 2019). In addition to clinically assigned SPMS three different classification methods were applied; method 1: modified real world EXPAND criteria (Kappos et al, Lancet 2018:391; 1263-1273), method 2: the data-derived definition from Melbourne University without the pyramidal Functional Systems Score (Lorscheider et al, Brain 2016:139; 2395-2405) and method 3: the decision tree classifier from Karolinska Institutet (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674).

Results

The SPMS proportions per registry, when comparing the clinically assigned SPMS with the results of the three classification methods, were CR: 8.8%, 21.3%, 22.1%, 25.0%; Denmark: 15.5%, 27.5%, 25.4%, 28.0%; Germany: 15.6%, 15.4%, 16.7%, 25.4%; Sweden: 23.7%, 20.8%, 23.2%, 24.6% and UK: 34.3%, 21.7%, 38.4%, 58.3% for clinical SPMS and methods 1, 2 and 3, respectively.

Conclusions

The proportion of clinically assigned SPMS patients varies between MS registries. When applying other classification methods, the SPMS proportion generally increases but remains variable between registries. As some of the classification methods have extensive requirements regarding data density, the number of unclassifiable samples created are considerable for some of the registries, which will influence the results. Providing a classification method that depends on objective information could prove useful when attempting to estimate the proportion of SPMS patients in MS populations but the choice of method may depend on the data characteristics of the individual MS registry.

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Epidemiology Poster Presentation

P0501 - The impact of socioeconomic status on the access to disease modifying therapy in people with multiple sclerosis. (ID 1507)

Speakers
Presentation Number
P0501
Presentation Topic
Epidemiology

Abstract

Background

Disease modifying therapies (DMTs) are unaffordable to many people with multiple sclerosis (MS) in privately funded health care systems. Evidence, to date, to support whether socioeconomic inequality in accessing DMTs for MS exists in publicly funded healthcare systems is equivocal.

Objectives

To examine whether access to DMTs for MS depends on the socioeconomic status (SES) using a geographically diverse population through the UK MS Register

Methods

The UK MS register, which was launched in 2011, aims to capture real world data about living with MS in the UK and collaborates with many hospitals across the country. We included all patients of working age with disease duration less than 6 years who were living in England and were diagnosed with relapsing remitting MS after the age of 29, between 2010 and 2017. SES was measured by their levels of education, financial resources and English index of multiple deprivation (IMD). IMD were divided into quintiles for the analysis. Any patients who did not provide information about their SES were excluded.

Results

A total of 1060 patients registered in the UK MS registry with mean age of 44 (standard error (SE), 0.25) years and mean disease duration of 2.34 (SE, 0.05) years were eligible. 819/1060 (77%) patients were female and 388/1060 (37%) patients received DMTs. We observed that people with MS who had postgraduate education had significantly better access to DMTs compared to secondary school attendees even when the analysis was adjusted for age, disease duration and financial resources. Access to DMTs did not depend upon whether the patients were employed, homemakers, receiving disability benefits, unemployed or retired. However, patients who worked in skilled and trade professions were less likely to receive DMTs compared to those who worked as managers, directors and senior officials with an odds ratio (OR) of 0.46 (95% confidence interval (CI), 0.22-0.96) even when the analysis was adjusted for education levels, age and disease duration. People who were less deprived were more likely to be treated with DMTs; OR for receiving DMT in the 5th IMD quintile (least deprived) was 1.96 (95% CI, 1.23-3.11) compared to 1st IMD quintile (most deprived), when adjusted for age and disease duration. The R2 value of these models showed that 3-5% of variation in accessing DMTs were dependent on these SES indices indicating that the influence of SES was small in our publicly funded national health service.

Conclusions

We found that the likelihood of receiving DMTs depend on the level of education, occupation and IMD suggesting that SES may influence the access to DMTs, in an English population.

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Internet and Social Media Poster Presentation

P0661 - A 164 second multi-format film successfully conveys the importance of early intervention in MS (ID 1031)

Speakers
Presentation Number
P0661
Presentation Topic
Internet and Social Media

Abstract

Background

Early treatment in MS is a complex concept to convey to a naïve audience as it often needs to be considered in the absence of symptoms. There are risks involved and other life priorities to contemplate.

Objectives

To address the importance of early intervention, a film was created conveying the results of non-action. The film was produced to appeal to a broad, modern audience: short duration (164 seconds), conceptual, without dialogue and accessible across multi-formats. We assessed its success at delivering the message to people with MS (pwMS) and a general population (GP).

Methods

Three populations were included: pwMS from the UK MS Register, pwMS from outpatient clinics and a GP (Ethical approval ref: 19/LO/0282). Based upon industry standard, pre-specified outcomes were 50% viewer retention (viewing for ≥30 seconds) and 50% understanding of the concepts. The film was embedded into a website, participants were asked to review the film and the four concepts were explained. Participants answered questions about the concepts and were asked for their opinion utilising free commentary and evaluated using thematic analysis.

Results

In the MS Register population 757/959 (78.9%) pwMS had total self-perceived understanding (4/4 concepts) versus 29/42 (69%) in pwMS from outpatients and 136/149 (91%) in the GP. Understanding in all cohorts were significantly above the expected outcomes (p<0.0001) and was highest in the GP compared to pwMS (p>0.0001) In the total population 714/1150 (62%) watched ≥30 seconds with an average viewing duration of 156/164 seconds (95%), significantly above the pre-specified outcome percent (p<0.0001). Nine-hundred and eighteen of 959 (96%) provided optional free text commentary about the film. Six-hundred and ten of 918 (66%) acknowledged the role of early intervention and of taking action. In a multivariate analysis with understanding as the factor, pwMS without degree-level education and who commentated neutrally/positively, were independently associated with increased understanding of the film.

Conclusions

As part of a preventative medicine strategy, a short duration, targeted film can successfully convey the importance of early intervention to both pwMS and a GP.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0739 - Optic chiasm involvement in MS, aquaporin-4 antibody-positive NMOSD, and MOG antibody-associated disease (ID 1441)

Speakers
Presentation Number
P0739
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Inflammatory demyelination in the anterior optic pathway, including the optic chiasm (OC), occurs frequently in relapsing-remitting multiple sclerosis (RRMS), aquaporin4 (AQP4) antibody (Ab) positive neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-Ab associated-disease (MOGAD).

Objectives

To evaluate the involvement of the OC in RRMS, AQP4-NMOSD and MOGAD using Magnetization Transfer Ratio (MTR) and explore its relationship with prior optic neuritis (ON).

Methods

We recruited 25 patients with RRMS (16 F, mean age: 44.6 yrs ±11.8, median EDSS: 2.0 [range: 1.0-7.5], mean number of previous episodes of ON: 0.44±0.58, 9 unilateral, 1 bilateral), 13 with AQP4-NMOSD (10 F, mean age: 45.3 yrs ±11.2, median EDSS: 3.0 [1.0-6.5], mean number of ON episodes: 1.54±1.13, 4 unilateral, 6 bilateral), 20 with MOGAD (13 F, mean age: 33.9 yrs ±16.4, median EDSS: 2.0 [0.0-6.5], mean number of ON episodes: 2.85±2.80, 6 unilateral, 11 bilateral) and 29 healthy controls (HC) (23 F, mean age: 35.9 yrs ±12.8). We used T2-weighted, MTon and MToff images to obtain MTR maps of the OC. Age-, sex-, and disease duration-adjusted linear regression models were used to compare the measures between disease and healthy groups (p<0.05).

Results

Chiasmal MTR values in patients with previous ON were lower in AQP4-NMOSD (p=0.040) and MOGAD (p=0.001) than HC but not when compared to patients without previous ON. In patients with RRMS and previous ON, MTR values were lower than patients without prior ON (p=0.003). No differences were found either between patients without ON and HC or between the disease groups.

When considering all patients with demyelinating diseases, patients with previous ON had lower chiasmal MTR values when compared to HC (unilateral: p=0.037; bilateral: p=0.002) and to patients without ON (unilateral: p=0.019; bilateral: p<0.001). This difference persisted when comparing both monophasic and relapsing ON patients to HC (p=0.044; p<0.001) and to patients without ON (p=0.019; p<0.001). No differences were found between patients without history of ON and HC. A correlation was found between MTR values and number of ON episodes (rho=-0.55, p<0.001).

Conclusions

Microstructural damage in the OC correlated with the number of ON episodes across inflammatory demyelinating diseases. A higher number of episodes is associated with lower chiasmal MTR, supporting its role as an accessible target for the assessment of the visual pathway in inflammatory diseases.

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Neuropsychology and Cognition Poster Presentation

P0807 - Evaluating cognitive functioning in Multiple Sclerosis, compared to other neurological disorders, using an online cognitive battery (ID 1716)

Speakers
Presentation Number
P0807
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Cognitive decline is a common, but poorly monitored, symptom of Multiple Sclerosis (MS). A promising approach to detect this decline is through online cognitive testing. Furthermore, cognitive decline may be similar between neurological conditions, suggesting diagnostic methods and treatments could overlap, yet how cognitive decline in MS relates to other conditions remains unknown.

Objectives

To evaluate how cognition is influenced by MS, compared to other neurological conditions, and assess the ability ofthe online cognitive battery ‘Great British Intelligence Test’ (GBIT) to measure these changes.

Methods

Data was collected from 56,829 controls, 236 patients with MS, 437 patients with Stroke, 104 patients with Traumatic Brain Injury (TBI) and 115 patients with Parkinson’s Disease (PD) who completed the GBIT and an in-depth questionnaire. A principal component analysis identified four components and scores were compared between disease cohorts and controls using one-way analysis of variance (ANOVA). Effect size (d), relative to controls, was reported for statistically significant findings (p<0.05).

Results

All neurological conditions had a lower overall cognitive score than controls (MS d = 0.31, Stroke d = 0.33, TBI d = 0.62, PD d = 0.62). In MS information processing speed (IPS) (d = 0.42) and spatial ability (d = 0.47) were the most affected domains, these were also negatively affected in other neurological conditions, while word memory and language ability were relatively spared. All disease cohorts except TBI also scored lower than controls in the emotion discrimination task (MS d = 0.24, stroke d = 0.18, PD d = 0.38); with the MS cohort scoring significantly lower than controls in six out of the 12 tasks in the GBIT.

Conclusions

In MS, cognitive decline was more domain specific compared to Stroke, TBI and PD. However, areas affected were similar between neurological disorders suggesting diagnostic methods and treatments could overlap. The current battery detected changes in cognition within MS, yet, future research is needed to optimize the battery for the MS population.

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Presenter Of 1 Presentation

Biostatistical Methods Poster Presentation

P0009 - ENTIMOS: a discrete event simulation model for maximizing efficiency of infusion suites in centres treating multiple sclerosis patients (ID 1630)

Speakers
Presentation Number
P0009
Presentation Topic
Biostatistical Methods

Abstract

Background

Multiple sclerosis patients are treated with intravenous (IV) disease modifying treatments (DMTs). Infusion suite resources are thus vital components of MS patient care. Infusion suites may be dedicated to MS patients, or shared with patients with other neurological conditions, or other patients requiring infusion. Here, we describe a resource utilization model for the infusion suites of Charing Cross (UK), which serves patients with different neurological conditions.

Objectives

To maximize the clinical efficiency of the infusion suite based on three resource constraints: percentage of patients IV MS DMTs, number of infusion chairs, and number of nurses. Efficiency gains in the infusion suite may benefit both patients and the healthcare system.

Methods

ENTIMOS, a discrete event simulation (DES) model, was created using SIMUL8 based on qualitative information from infusion centers and populated with data specific to the Charing Cross hospital neurology infusion suite. Posology, administration information, and rates of immune related-reactions (IRRs) were applied from published data sources from both MS and non-MS DMTs of interest.

The infusion suite model assumes 75 MS and 21 non-MS patients weekly, including up to seven MS patients initiating IV treatment; is equipped with 12 infusion chairs and six beds; and is staffed with a total of six nurses. We simulated the effects of changing the three resource constraints described on the number of patients waiting for an appointment (queue size), the time for patients to get an appointment for their first or subsequent IV treatments (waiting times), and general resource utilization.

Results

Changing the number of chairs, moving a subset of patients from IV to any non-IV alternative treatments, moving patients between MS IV treatments, or changing the allocation of nurse resources may all have an impact on the queue size and waiting times. Once the changes are implemented in the model, existing resources optimised and the queue size reduced, the effective centre throughput can be increased.

Conclusions

ENTIMOS allows users to optimize their use of constrained resources in an infusion suite to improve patient experience and infusion suite efficiency.

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