Rostock University Medical Center
Department of Neurology

Author Of 4 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0030 - Association of average blood cell telomere length with the clinical course of MS over a 10-year period (ID 352)

Speakers
Presentation Number
P0030
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Aging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS.

Objectives

The aim of this study was to evaluate the length of telomeric DNA sequences in peripheral blood in relation to clinical MS phenotypes and disease progression.

Methods

We measured the average leukocyte telomere length (LTL) in biobanked samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS) and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistics and regression models adjusted for age and sex.

Results

The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up period.

Conclusions

Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between age- and disease-related immune system alterations and blood cell telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained by exploring the distribution of telomere lengths in specific cell populations.

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Diagnostic Criteria and Differential Diagnosis Poster Presentation

P0263 - Serum neurofilament predicts clinical progression and increases diagnostic accuracy in patients with early multiple sclerosis (ID 1336)

Abstract

Background

Up to date prognostic estimation in newly diagnosed patients is hardly possible while the differentiation between disabling versus more benign courses is of utmost relevance. Reliable blood-based biomarkers that are associated with diagnosis and prognosis of multiple sclerosis (MS) have not been established.

Objectives

Can serum neurofilament light chain measurements serve as a reliable biomarker for diagnostic accuracy and prognosis for multiple sclerosis patients at the time point of diagnosis?

Methods

In a multicenter prospective longitudinal observational cohort, patients with a first diagnosis of multiple sclerosis (MS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers and assessed yearly with a standardized protocol. Patients were offered standard immunotherapies according to national treatment guidelines. Serum NfL concentrations were measured using an ultrasensitive single-molecule array (Simoa).

Results

A possible association between sNfL levels and clinical diagnosis, relapses, MRI parameters and treatment decisions was tested in 814 patients classified according to current (2017) and older (2010) McDonald criteria at time point of diagnosis and two years after study inclusion sNfL levels correlated with number of T2 and Gd+ lesions and clinical relapses. After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036) and increased accuracy of distinction between CIS and RRMS, when including ≥ 90th percentile of sNfL values. Patients receiving disease-modifying treatment (DMT) during the first two years had higher sNfl baseline levels (11.8 pg/ml, 7.5-20.9 pg/ml, n = 727) than patients never receiving DMT (9.5 pg/ml, IQR 6.4-14.1 pg/ml, n = 87, p = 0.002). Longitudinal sNfL levels reflected treatment decisions within the first four years.

Conclusions

sNfL is associated with diagnosis and prognosis of MS patients at the time point of first diagnosis and may be of use for initial treatment stratification.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0315 - Disease modifying therapies in patients with aggressive MS (ID 1510)

Speakers
Presentation Number
P0315
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There is a growing need to identify the course of aggressive multiple sclerosis (agMS) at an early stage so that affected patients can be treated with suitable disease modifying drugs (DMD). Investigations of treatment patterns in agMS and non-agMS patients are of interest, particularly in the context of the multitude of agMS definitions.

Objectives

We aimed to determine characteristics of DMDs at baseline for comparative analyses of agMS patients and non-agMS patients.

Methods

We included patients from the German Multiple Sclerosis registry who started DMD use between 2010 and 2020 and were assessable on whether they are agMS patients according to a commonly used criterium of reaching EDSS ≥6.0, or by a criterium for highly active MS, i.e. ≥2 relapses during 12 months, or gd+ lesions on MRI. Both were assessed within the first 5 years of disease duration.

Results

7249 patients fulfilled the inclusion criteria. Of these, 860 were identified as agMS. In agMS patients, Interferons (INFs) were the most frequently used DMDs with 34.8% followed by Glatiramer acetate (GLAT, 24.0%), Dimethyl fumarate (DMF, 15.8%), Teriflunomide (TRF, 7.6%), Natalizumab (NTZ, 5.4%), Fingolimod (FTY, 3.9%), Ocrelizumab (OCR, 3.2%), Steroids (STE, 1.8%), and others (3.5%). Regarding patients with non-agMS, INFs were also most frequent with 30.5% followed by GLAT (18.1%), DMF (13.2%), FTY (8.1%), NTZ (7.7%), TRF (7.5%), OCR (5.9%), STE (2.3%), and others (6.7%).

Within 5 years of disease duration, switches to another DMD were observed for 51% of agMS patients whereas only 17% of non-agMS switched to a second DMD. The average time spent on the first DMD was 1.3 (±1.1) years for agMS patients and 3.4 (±3.6) years for non-agMS patients (p<0.001; Mann-Whitney test). With regard to DMD use, significant differences between agMS and non-agMS patients were detected (p<0.001; χ2-test): INFs (p=0.009), GLAT (p<0.001) and DMF (p=0.03) were used significantly more often by agMS patients while FTY (p<0.001), NTZ (p=0.02) and OCR (p=0.002) were used more often by non-agMS patients.

Conclusions

Our analysis showed that in line with the (national) guidelines, the new immunomodulatory treatments are accessible to all MS patients. The patients classified as agMS spent less time on the first DMD than non-agMS patients did. To investigate causal factors in the connection between DMD preference and resulting disease progression, Marginal Structural Models are required, adjusting for relevant time-varying confounders such as patient demography, clinical visit details, MRI, and relapse parameters.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0707 - Costs and health-related quality of life in patients with neuromyelitis optica spectrum disorder and MOG-antibody associated disease (CHANCENMO-Study) (ID 1015)

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOG-AD) are orphan diseases with high impact on quality of life and to date unknown socio-economic burden.

Objectives

The aim of this study was to evaluate costs and health-related quality of life of NMOSD and MOG-AD from the societal perspective.

Methods

In a multicenter cross-sectional study throughout Germany between 04/2017 and 04/2019, the primary data on retrospective consumption of medical and non-medical resources and work ability related to NMOSD and MOG-AD were assessed via standardized and pre-tested paper-based patient questionnaires. Health-related quality of life was captured by the EuroQoL Group EQ-5D-5L questionnaire. Clinical data were retrieved from the Neuromyelitis Optica Study Group (NEMOS) database. Patient recruitment took place at 17 German NEMOS centers. Costs were analyzed in EUR for 2018.

Results

During the recruitment period, 218 of 275 adult patients were screened for eligibility. 212 patients (80.2% women; mean age 49 ± SD 15 years; mean disease duration 9 ± SD 8.5 years; Expanded Disability Status Scale (EDSS) 3.7 ± SD 2.1) were analyzed. The mean total annual per capita cost of illness accounted for EUR 59 576 and the mean index value of the EQ-5D-5L was 0.693. Given an estimated prevalence of NMOSD in Germany of 1.3/100 000, the annual burden from the societal perspective adds to EUR 64.3 Mio for Germany. The most important cost drivers were informal care costs (27.6% of total costs), indirect costs (23.3%; particularly loss of salary) and drugs, especially immunotherapeutics (16.4%). Costs showed a significant positive correlation with disease severity (p<0.0001); in the EDSS 6.5-8.5 subgroup the annual costs were EUR 129 436. Moreover, the health-related quality of life revealed a negative correlation with disease severity (p<0.0001); in the EDSS 6.5-8.5 subgroup the mean index value was 0.195.

Conclusions

These German data from the era without approved standard medications show enormous effects of the disease on costs and quality of life and might be helpful for estimating the impact and cost-effectiveness of new therapeutic approaches.

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