Hospital Universitario Ramón y Cajal
Immunology

Author Of 5 Presentations

Epidemiology Poster Presentation

LB1166 - Risk and outcomes of COVID-19 in patients with multiple sclerosis in Madrid Spain  (ID 1480)

Abstract

Background

Infections are an important cause of hospitalization in patients with MS. Data on outcomes of COVID-19 in patients with MS are limited

Objectives

To quantify the risks of infection, hospitalization, admission to intensive care and death due to SARS-CoV-2 infection among patients with MS relative to the general population, and to identify factors associated with risk of hospitalization

Methods

A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit (ICU) admission and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison.

Results

Two-hundred nineteen patients with MS were included in the registry, 51 of whom were hospitalized. The infection incidence rate (IR) was lower in patients with MS than the general population (adjusted IR ratio 0.78; 95% confidence interval: 0.70–0.80), but hospitalization rates were higher (adjusted relative risk 6.52 [6.13–7.04]). Disease severity was generally low, with only one ICU admission and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying therapy (DMT) and hospitalization risk.

Conclusions

Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue DMT should be based on a careful risk-benefit assessment.

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Biomarkers and Bioinformatics Poster Presentation

P0066 - Dimethyl fumarate decreases serum neurofilament light chain in relapsing-remitting multiple sclerosis patients. (ID 924)

Presentation Number
P0066
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Serum neurofilament light chain (sNfL) levels are associated with disease activity and prognosis in relapsing-remitting multiple sclerosis (RRMS) patients. Treatment with second-line disease modifying therapies (DMTs) leads to a reduction of sNfL, but little is known regarding first-line DMTs as dimethyl fumarate (DMF).

Objectives

To explore changes of sNfL levels in RRMS patients during treatment with DMF. To evaluate the potential role of sNfL measurement to predict an optimal treatment response.

Methods

Blood samples from 64 consecutive RRMS patients initiating DMF at Hospital Universitario Ramón y Cajal were collected at baseline and at 3, 6 and 12 months thereafter. sNfL levels were measured using a sensitive Single Molecular Array (SIMOA) assay (Quanterix). Patients were classified into No Evidence of Disease Activity (NEDA) and Ongoing Disease Activity (ODA) according the presence/absence of relapses, EDSS progression and/or MRI activity during the first year.

Results

Age at treatment initiation was 40.6 [33.2-46.3] years (median [25-75%IQR]) and EDSS was 1.5 [1.5-2.5]. Forty eight (75%) patients received other previous DMTs, seven of them were second-line DMTs. 66% of patients had evidence of disease activity at DMF initiation. Baseline sNfL levels were higher in patients who had evidence of disease activity at that time compared with patients who had not (12.2 pg/ml Vs. 8.8 pg/ml, p=0.024). No differences were found in baseline sNfL levels between naïve and previously treated patients, or between patients treated with first and second line DMTs. After 12 months of DMF treatment, 44 (69%) patients were NEDA and 20 (31%) were ODA. Baseline sNfL levels were higher in ODA patients compared to NEDA patients (14.6 pg/ml Vs. 9.2 pg/ml, p=0.016). A cut-off value of 12 pg/ml was established to predict NEDA status (OR=4.7; 95%CI: 1.6–15.7; p=0.008). After one year of DMF, sNfL levels decreased by 34.4% (p<0.0001). Both NEDA and ODA patients experienced a progressive sNfL reduction during the first year of treatment. However, this reduction was observed earlier in NEDA patients (three months after DMF initiation) than in ODA patients (six months).

Conclusions

DMF induced a progressive decrease in sNfL concentration during the first year of treatment. This reduction was delayed in ODA patients. Patients with basal sNFL values ≤ 12 pg/ml showed increased probability to achieve NEDA status at 12 months.

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Biomarkers and Bioinformatics Poster Presentation

P0172 - The prognostic value of lipid-specific IgM oligoclonal bands versus IgM index in patients with a clinical isolated syndrome: a comparative study. (ID 1114)

Speakers
Presentation Number
P0172
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

The value of intrathecal IgM synthesis (ITMS) is increasingly recognized as a prognostic biomarker in patients with a clinically isolated syndrome (CIS). However, no comparative studies between different methods to assess ITMS have been described previously evaluating the prognosis of patients with CIS.

Objectives

To compare the predictive value of IgM Reibergram (IR) and the presence of lipid-specific IgM oligoclonal bands (LS-OCMB) in CSF to predict conversion to clinically defined multiple sclerosis (CDMS), and the onset of EDSS of 3, 6 and a secondary progressive MS (SPMS).

Methods

An observational single-center study with CIS patients with at least 2 years of follow-up attended at Hospital Universitario Ramón y Cajal was performed. Demographics, clinical, radiological and immunological variables were collected.

Results

196 patients were included, 131 (66.8%) women, with a median (range) age of 31 (12–63) years and mean (SD) follow-up of 13.2 (±7.0) years. Overall, positive LS-OCMB was observed in 52 (26.5%) patients and IR in 32/193 (16.6%), reaching a concordance of 59.4% between both. The risk of CDMS was significantly higher exclusively among LS-OCMB (adjusted HR 1.80 (95%CI 1.24-2.62), p=0.002), but not for IR. In addition, LS-OCMB predicted a higher risk of reaching an EDSS of 3 (OR 1.97, p=0.044), an EDSS of 6 (OR 3.82, p=0.001) and a SPMS (OR 2.67, p=0.013) among MS patients. No significant differences were observed with IR.

Conclusions

LS-OCMB are a more sensitive and reliable CSF biomarker to predict the natural history of CIS patients compare to semi-quantitative IR.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0327 - Effectiveness and safety profile of the Natalizumab extended interval dosing in a Spanish cohort (ID 1815)

Presentation Number
P0327
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Previous Biogen analyses of the US TOUCH Registry showed that the risk of developing natalizumab-associated progressive multifocal leukoencephalopathy (PML) among anti-JCV antibody positive natalizumab-treated patients was significantly lower with extended interval dosing (EID) compared with standard interval dosing (SID). However, the efficacy of EID was not evaluated in these analyses. Real-world studies and modelling data suggest that a patient population stable on natalizumab SID who is then switched to EID is more likely to maintain efficacy with EID as compared to a population who initiates natalizumab on EID.

Objectives

The main objective of the study is to evaluate the effectiveness (measured by the annualized relapse rate - ARR) of natalizumab EID in subjects who have been previously treated with natalizumab SID during the 12-month list, in relation to continuous SID treatment.

Methods

Observational, open-label study with retrospective analysis of a prospective cohort of patients with relapsing-remitting multiple sclerosis (RRMS) treated at Hospital Ramón y Cajal (Madrid) with natalizumab for 12 months using SID (Infusion every month). All patients were transferred after a period of initial treatment at standard interval doses to a 6-week EID, according to hospital protocol, eliminating a potential selection bias for assigning less active patients to the EID group Demographic, clinical, radiological and immunological variables were collected.

Results

61 patients were included, 33 (54%) women, with a median (range) age at treatment initiation of 35 (17-55) years. Median (range) treatment duration was 5,2 years (2-11,3), 3,47 years (1,4-7,8) in SID, 1,7 years (0,5-4,1) in EID. There was no difference in ARR, mean [95% confidence interval (CI)], (SID: 0.05 [0,01-0,1]; EID: 0.02 [0,02-0,05]; P=0.558), or EDSS (SID: 2,35 [1,9-2,7], EID: 2,67 [2,2-3,9]; p=0,42).

Conclusions

This study does not demonstrate significant differences in relapse outcomes between SID and EID periods of patients who switched to EID from natalizumab after ≥1 year on SID. These results are consistent with previous analyzes without comparison that concluded that efficacy is maintained after switching to EID. Consistent MRI and EDSS results will be shown in the final poster. An ongoing prospective randomized trial of EID versus SID will provide a more complete understanding of the effectiveness of natalizumab EID.

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Pathogenesis – Immunology Poster Presentation

P0975 - Lipid-specific oligoclonal IgM bands condition age-related changes in multiple sclerosis (ID 1396)

Abstract

Background

Age has high influence on clinical course of chronic inflammatory diseases such as multiple sclerosis (MS). Lipid-specific oligoclonal IgM bands (LS-OCBM) in cerebrospinal fluid (CSF) of MS patients are biomarkers of high inflammatory disease. However, the relationship between both variables has not been fully studied.

Objectives

To explore age-related changes in CSF of MS patients leading to senescence and to study the role of LS-OCBM in this process.

Methods

A prospective cross-sectional study of 263 MS patients followed at Ramon y Cajal University Hospital, Madrid. Seventy-two showed (M+) and 191 (M-) lacked CSF LS-OCBM. We explored CSF immune cells, soluble mediators, microRNAs and clinical data.

Results

MS patients older than 45 years (O45) showed significant rises in CSF Programmed death ligand 1 (PD-L1; p=0.001) and T-cell immunoglobulin mucin-3 (TIM-3; p<0.0001), which induce lymphocyte tolerance, and in Chitinase 3-like-1 (p<0.0001) and Activin-A (p<0.0001), which lead to innate cell activation. This associated with low values of pro-inflammatory B cells and of Th17 lymphocytes. In addition, M- O45 patients experienced significant increases in miR-125b-5p (p=0.01) and miR-145-5p (p=0.02), two miRNA associated with immune senescence, an increase of let-7b-5p (p=0.01) that counteract innate-cell activation, a dramatic decrease of CSF lymphocytes (p<0.0001) and of NK cells (p=0.002) and increased serum anti-cytomegalovirus antibodies (p=0.009). However, M+ O45 patients exhibited a reduction of miR-204-5p (p=0.01), that induce innate-cell activation and increased CSF levels of superoxide dismutase (p=0.04) and isoprostane (p=0.03), markers of oxidative stress. These changes resulted in increased Multiple Sclerosis Severity Score (MSSS) on M+ O45 patients.

Conclusions

M- O45 MS patients showed inhibition of the intrathecal adaptive immune response and early immunosenescence. Conversely, M+ O45 MS patients displayed intrathecal innate cell activation and accelerated disability worsening. These data could be relevant for treating aged MS patients.

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