Complejo Hospitalario Universitario de Vigo
Department of Neurology

Author Of 3 Presentations

Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0324 - Effect of ocrelizumab treatment in peripheral blood leukocyte subsets of Primary Progressive Multiple Sclerosis patients (ID 1613)

Abstract

Background

Ocrelizumab is the first drug approved as disease modifying treatment for primary progressive (PP) multiple sclerosis (MS). As a humanized monoclonal antibody targeting CD20 cells, it is widely known that ocrelizumab treatment results in B cells depletion, but less is known about the effects of this drug in other blood leukocyte subsets of PPMS patients.

Objectives

To explore the changes induced by ocrelizumab in blood immune cells of PPMS patients to further understand their effects in the abnormal inflammatory response.

Methods

Multi-centre prospective longitudinal study including fifty‐three PPMS patients who initiated ocrelizumab treatment. Effector, memory, and regulatory cells were analyzed by flow cytometry at baseline and after 6 months of treatment. To assess differences between baseline and after 6 months, Wilcoxon matched paired tests were used and p values were corrected using Bonferroni test.

Results

Ocrelizumab decreased numbers of naïve and memory B cells (p<0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha (p<0.0001 in all cases). A reduction of CD20+ T cell numbers (p=0.02) and percentages (p<0.0001) was also observed. We also detected a clear remodelation of the T cell compartment characterized by relative increases of the naïve/effector ratio in CD4+ (p=0.002) and CD8+ (p=0.002) T cells, and relative decreases of CD4+ (p=0.03) and CD8+ (p=0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p=0.002), with no changes in those producing inflammatory cytokines. All these changes resulted in a reduction of serum neurofilament light chain (sNfL) levels (p=0.009).

Conclusions

Effector B cell depletion by ocrelizumab treatment induces changes in the T cell response of PPMS patients towards a low inflammatory profile. This resulted in a decrease of sNfL levels.

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Pathogenesis – Immunology Poster Presentation

P0964 - Herpesvirus serology in primary progressive multiple sclerosis (ID 919)

Abstract

Background

Viruses have been involved in multiple sclerosis (MS) in last years. However, almost all of the studies published so far have focused on patients with relapsing-remitting MS (RRMS), with no data about viruses in patients with progressive primary MS (PPMS). Due to the differences that exist between these two forms of MS it would be interesting to know if there is also differences regarding viruses previously related to the etiopathogenesis of the disease.

Objectives

The aim of this study was to analyze the prevalence and titters of different viral antibodies: IgG against EBNA-1 and VCA of Epstein-Barr virus (EBV), IgG and IgM against Human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), in PPMS patients and to compare those results with other cohort of RRMS patients.

Methods

A total of 166 MS patients were recruited: 71 with PPMS and 95 with RRMS (mean age: 48 and 43.6 years, respectively; gender: 47.9% and 61% female, respectively). We analyzed the presence and titters of the antibodies above mentioned with ELISA commercial kits, following manufacturer instructions.

Results

1. Herpesvirus prevalences: we only found a statistical significant difference for IgG antibodies against EBNA-1 of EBV (84.5% of PPMS patients were positive vs. 97.8% of RRMS patients; p=0.002). When we analyzed these prevalences by age groups (<45 and >45 years), we only found statistical significant differences between PPMS and RRMS patients under 45 years: 84.6% of PPMS patients were positive for IgG against EBNA-1 vs. 100% of RRMS patients (p=0.015), and 26.9% of PPMS patients were positive for IgM against HHV-6 vs. 7.7% of RRMS patients (p=0.021). 2. Herpesvirus titters: we found that IgG titters against CMV were higher among PPMS patients than in RRMS patients (31.3 AU vs. 16.01 AU, p=0.0001); IgG titters against HHV-6 were also higher in PPMS patients (29.3 AU vs. 20.5, p=0.004); IgG titters against EBNA-1 of EBV were lower in PPMS patients than in RRMS patients (16.4 AU vs. 22.8 AU, p<0.0001).

Conclusions

We have found statistical significant differences between different herpesvirus prevalences and titters between PPMS and RRMS patients that should be deeper studied to evaluate their possible contribution to the existing differences between these two forms of MS.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1050 - Quantifying the patient´s perspective in neuromyelitis optica spectrum disorders: Design of a multicenter, non-interventional study (ID 222)

Abstract

Background

Patients with neuromyelitis optica spectrum disorders (NMOSD) experience a spectrum of symptoms negatively impacting on daily living and quality of life. The systematic assessment of patient perspectives has the capacity to provide crucial clinical information that could otherwise be lost when relying on clinical evaluation alone. However, the patient experience living with NMOSD is limited, in particular implementing standardized patient-reported outcomes (PROs).

Objectives

The primary objective of this study protocol is to assess the health-related quality of life and well-being of NMOSD patients.

Methods

A multicenter, non-interventional, cross-sectional study will be conducted with patients diagnosed with NMOSD (2015 Wingerchuk criteria) (PERSPECTIVES-NMO Study). Primary outcomes measures will be the 29-item Multiple Sclerosis Impact Scale and the Satisfaction with Life Scale. Demographic characteristics, clinical and imaging outcomes will be collected, including the number and type of attacks, antibody status, Expanded Disability Status Scale score, Nine-Hole Peg Test, Timed 25-Foot Walk, and Magnetic Resonance Imaging findings. Cognition will be evaluated using the Rao Brief Repeatable Neuropsychological Battery. Additional outcomes from the patient´s perspective (PROs) will be collected, including symptoms severity (SymptoMScreen questionnaire), fatigue (Fatigue Impact Scale for Daily Use), pain (MOS Pain Effects Scale), mood (Beck Depression Inventory-Fast Screen), perception of stigma (8-item Stigma Scale for Chronic Illness), and work-related difficulties (23-item Multiple Sclerosis Work Difficulties Questionnaire).

Results

Patient recruitment began in December 2019 with a planned total sample of 70 patients. The study is currently ongoing.

Conclusions

The study results are expected to provide meaningful insights into the clinical burden of disease. A better understanding of patient experiences may foster the development of patient-centered specific plans and more targeted rehabilitation in clinical practice.

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