Hospital Arnau de Vilanova
Neurología

Author Of 4 Presentations

Disease Modifying Therapies – Risk Management Poster Presentation

LB1165 - COVID-19 in cladribine-treated patients with Multiple Sclerosis (ID 1470)

Speakers
Presentation Number
LB1165
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

The emergence of a new coronavirus (COVID-19) and the subsequent pandemic present a unique challenge to neurologists managing patients with multiple sclerosis (MS). Preliminary reports do not support an increased risk of severe outcome associated with disease modifying therapies (DMTs) but real-world evidence is lacking.

Objectives

To describe our experience in 14 patients with MS who have been affected by SARS-CoV-2 (with a clinical, RT-PCR, or serological diagnosis) and who were being treated with cladribine in Spain.

Methods

We conducted a consecutive clinical series study including cases occurred in Spain since January 31, 2020 when the first COVID-19 patient was detected in Spain until the end of June 2020.

Results

Patients were mostly female (64%), with an average age of 40.1 (± 12.0) years and a disease duration of 9.7 (± 8.9) years. Median EDSS was 1 (IQR 0–2.5), and the average time on treatment with cladribine was 7.7 (±5.77) months. Two patients had grade 1 lymphopenia, five patients had grade 2 lymphopenia, one patient had grade 3 lymphopenia and six patients were in normal range. Only 1 patient required hospitalization. None required ICU care, or intubation. 93% of the patients improved without any specific treatment. 2 patients (14%) were asymptomatic, 11 (79%) were mild and 1 (7%) was moderate. All recovered without sequelae. 7 of the patients (50%) had a serology test done that showed presence of anti-viral antibodies of IgG and IgM type in all cases.

In our series the patients had a favorable evolution, and all recovered. Factors that could have influenced those results could be the age of the patients, the lack of other risk factors and the mechanism of action of cladribine. It is known that the limited activity of cladribine on cells of the innate immune system and its relatively minor impact on CD8 T cells and plasma cells may have implications for maintained protection from bacterial and viral infections. Importantly, cladribine CD4+ T cell and B cells depletion is partial and transient. The short-term dosing regimen of oral cladribine, potentially reduces depleting effects on the innate immune system.

Conclusions

From this limited number of patients our observations suggest that cladribine treatment does not appear to worsen COVID-19 disease prognosis. MS is a debilitating disease and discontinuing effective treatments might have adverse consequences, benefit/risk assessment is crucial in the current context. Our patients treated with cladribine had an adequate resolution of COVID-19 and mounted an immune response, however more studies are necessary to confirm and extend our preliminary findings.

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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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Disease Modifying Therapies – Risk Management Poster Presentation

P0401 - Switching disease modifying treatment in relapsing multiple sclerosis: Delphi consensus of the Demyelinating Group of the Spanish Society of Neurology (ID 234)

Speakers
Authors
Presentation Number
P0401
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

The increasingly number of available Disease Modifying Therapies (DMTs) have led to enhanced perspectives for treating relapsing multiple sclerosis (RMS). The different DMTs have greatly contributed for a more personalized treatment approach with improved clinical outcomes. Currently the DMT landscape makes the decision to switch between different options complex - considering both their different clinical profiles and patient characteristics, especially in absence of unified recommendations for switching.

Objectives

The Demyelinating Expert Group of the Spanish Society of Neurology (SEN) considered to carry out a consensus project with the objective of answering critical questions about DMT sequencing for an optimal patient management.

Methods

After an exhaustive literature review, the expert group identified 5 main topics to integrate the proposed questions: I) treatment objectives and risk-benefit balance; II) reasons for switching; III) suboptimal response definition; IV) strategies for treatment change; V) washout periods. Delphi´s methodology was used for assessing the level of agreement among the discussed statements.

Results

The expert group workshops leaded to formulate a total number of 106 final statements to cover the defined 5 main topics. From them, consensus (at least 80% of agreement between participants) was reached in 99 responses (93%), while 7 (7%) were finally discarded for lack of agreement.

Conclusions

These Spanish Neurologists´switching recommendations addressed DMT sequencing difficulties that clinicians face in MS clinical practice. Evidence from reviewed literature added to Spanish MS experts´clinical experience resulted in those basic guidelines that will optimize DMT use and patient management in Spain.

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Neuropsychology and Cognition Poster Presentation

P0821 - Prevalence data of Cognitive Impairment in patients with Multiple Sclerosis of good clinical evolution in a cohort of patients from the city of Lleida (ID 1408)

Speakers
Presentation Number
P0821
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Cognitive impairment (CI) appears in approximately 50% of cases with Multiple Sclerosis (MS), but we do not know how to determine the moment of this phenomenon and it is not associated with physical disability of the disease.

Objectives

We set out to describe the prevalence of CI of the patients in our cohort who are defined as patients with good evolution by their clinical characteristics.

Methods

A cross-sectional study was conducted recruiting a total of 174 patients, of whom 111 had disease modifying treatments (DMT) (only first line treatments) and 63 patients without DMT (noDMT) and 69 healthy controls (HC) (recruitment not completed). All patients had to have an EDSS between 0 and 3.0 and a minimum of 5 years of evolution of the disease. All performed a neuropsychological examination that included a battery of tests to evaluate all cognitive domains (cutoff point percentile <5) and were classified as: normal or cognitive impairment and mild, moderate and severe according to the number of failed tests in each cognitive domain.

Results

When we compared the patients vs the HC, we observed statistically significant differences p <0.019, regarding the general cognitive impairment (CI in controls: 19%; CI patients: 34%). The main difference between patients and HC was observed in the verbal memory domain p <0.014. When comparing patients with DMT with noDMT patients, we did not observe statistically significant differences between the groups (p <0.241), the percentages of patients with cognitive impairment were 31% for DMT patients and 40% in the group of patients without DMT. No significant differences were observed between the MS groups regarding the prevalence of mild, moderate or severe cognitive impairment.

Conclusions

Patients with good MS evolution have a higher prevalence of cognitive impairment than the normal population despite low physical disability and there is no difference between patients with DMT and patients without DMT with the same characteristics.

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Presenter Of 1 Presentation

Disease Modifying Therapies – Risk Management Poster Presentation

P0401 - Switching disease modifying treatment in relapsing multiple sclerosis: Delphi consensus of the Demyelinating Group of the Spanish Society of Neurology (ID 234)

Speakers
Authors
Presentation Number
P0401
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

The increasingly number of available Disease Modifying Therapies (DMTs) have led to enhanced perspectives for treating relapsing multiple sclerosis (RMS). The different DMTs have greatly contributed for a more personalized treatment approach with improved clinical outcomes. Currently the DMT landscape makes the decision to switch between different options complex - considering both their different clinical profiles and patient characteristics, especially in absence of unified recommendations for switching.

Objectives

The Demyelinating Expert Group of the Spanish Society of Neurology (SEN) considered to carry out a consensus project with the objective of answering critical questions about DMT sequencing for an optimal patient management.

Methods

After an exhaustive literature review, the expert group identified 5 main topics to integrate the proposed questions: I) treatment objectives and risk-benefit balance; II) reasons for switching; III) suboptimal response definition; IV) strategies for treatment change; V) washout periods. Delphi´s methodology was used for assessing the level of agreement among the discussed statements.

Results

The expert group workshops leaded to formulate a total number of 106 final statements to cover the defined 5 main topics. From them, consensus (at least 80% of agreement between participants) was reached in 99 responses (93%), while 7 (7%) were finally discarded for lack of agreement.

Conclusions

These Spanish Neurologists´switching recommendations addressed DMT sequencing difficulties that clinicians face in MS clinical practice. Evidence from reviewed literature added to Spanish MS experts´clinical experience resulted in those basic guidelines that will optimize DMT use and patient management in Spain.

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