Author Of 3 Presentations
FC03.01 - Defining controversies of benign MS using digital technology
Abstract
Background
Multiple-Sclerosis-Partners-Advancing-Technology-Health-Solutions (MSPATHS) is an international multicentre digital database that collects clinical information provided directly by patients together with standardized MRI and biomarkers.
Objectives
We identify a Benign multiple sclerosis (BMS) population using Patient-Determined-Disease-Steps (PDDS) as a proxy for EDSS. We describe its physical and non-physical characteristics, and explore the features that best discriminate BMS.
Methods
Cross-sectional study of MSPATHS patients (Feb 2019). In patients with disease duration ≥10 years, BMS was considered when PDDS score<2. We compared BMS and non-BMS in terms of (1)socio-demographic and clinical characteristics, (2)physical status (lower and upper extremity function by Neuro-QoL (LUEF-NQ) and neurological performance tests: walking speed test (WST), manual dexterity test (MDT), processing speed test (PST), contrast sensitivity test (CST)) and non-physical symptoms (anxiety, depression, fatigue, among other NQ domains), and (3)MRI (gadolinium enhancement and new T2 lesions). We built a random forest model to estimate the importance of each variable. Cohen’s d was used for descriptive statistics to categorize differences in small (d=0.2-0.5), medium (d=0.5-0.8) and large (d>0.8). A sensitivity analysis with a 1:1 matched cohort by disease duration was performed.
Results
From 15,257 patients included, 8,349 had a disease duration ≥10 years and 3,852 (46.1%) were classified as BMS. (1)BMS and non-BMS patients were similar for gender, age at disease onset and diagnosis, ethnicity, years of education and smoking status. Compared to non-BMS, BMS had small differences in disease duration (median, 17.2 (12,9-23,4) vs. 20.9 (15,1-28,8 years); d=0.39) but medium/large differences in (2)physical status (LUEF-NQ d=2.06 and 1.53, WST d=0.81, MDT d=0.97, PST d=0.82 and CST d=0.56), as well as, in all non-physical symptoms evaluated by NQ (anxiety d=0.53, depression d=0.69, fatigue d=0.84, stigma d=1.32, cognition d=0.69, social role satisfaction (SRS) d=1.11 and participation (SRP) d=1.19). (3)No differences were found on MRI activity. With 0.88 sensitivity and 0.86 specificity, LUEF-NQ was the most contributing variable for the random forest followed by stigma, SRP, WST, and SRS. The sensitivity analysis showed similar results.
Conclusions
PDDS seems to be a useful disability proxy to identify BMS when using digital technology. LUEF-NQ, stigma, SRP and SRS seem to better discriminate BMS.
PS01.05 - Rituximab treatment for MS: an observational multicentric dose comparison
Abstract
Background
Rituximab (RTX) is an anti-CD20 monoclonal antibody, widely used as an off-label treatment for multiple sclerosis (MS). Despite well-known efficacy and safety, RTX regimen has not yet been standardized.
Objectives
We aimed to compare efficacy and safety data of two different rituximab doses at two large Catalan multiple sclerosis centres.
Methods
A two-centre ambispective study considering all MS patients that have received at least one RTX cycle until February 2020 was conducted. In Barcelona centre (BC), RTX regimen used was 2g intravenously (IV), at least during 3 cycles, followed by 1g every 6 months, while in Girona centre (GC), was 2g IV, at least the first cycle, followed by 500mg every 6 months. Patients were clinically followed every 6 months with lab tests, and brain MRI scans were performed at baseline and yearly thereafter. Baseline clinical, radiological and demographic characteristics were collected. Annual relapse rate (ARR), contrast-enhancing lesions (CELs) and new T2 lesions at one and third year on treatment, as well as EDSS changes at last follow-up visit, were evaluated. Also, the dynamics of CD19% lymphocytes and IG immunoglobulin (IgG) values in serum, as well as the incidence of adverse events (AE) were described.
Results
A total of 303 patients (249 at BC and 54 at GC) were included. Main reason to start RTX was clinical progression plus inflammatory activity (clinical, radiological or both) (45.8% BC vs 79.6% GC). No differences on age at RTX onset, gender and disease duration were found between both centres. At baseline, mean ARR was 0.37±0.6 (BC) vs. 0.33±0.5 (GC); median EDSS was 5.5 (1-9.0) (BC) vs. 6.0 (1-8.0) (GC); and proportion of MRI with CELs was 32.4% (BC) vs. 42.6% (GC). ARR decrease to 0.05 (87.5%, p<0.001) for BC vs. 0.03 (90.3%, p=0.018) for GC at first year, and to 0.08 (88.3%, p=0.016) vs. 0 (100%, p=0.172) at third year. Considering only progressive MS phenotypes, 79.4% vs. 71.4% of patients remained stable or improved the EDSS. Regarding MRI findings, percentages of patients with CELs and new T2 lesions (BC vs GC) were 2.7% vs. 8% and 19% vs. 16% at one year; and 0% vs. 0% and 12% vs. 0% at third year. AE incidence was higher at BC during the first year (14.8% vs 4.1%). No difference in the dynamics of CD19% lymphocytes was found, while IgG values decreased significantly in the BC cohort throughout the first 3 years.
Conclusions
In the treatment of multiple sclerosis, low doses of rituximab seem to offer similar effectiveness with better safety profile than high doses.
PS09.03 - Predictive biomarkers of the development of autoimmunity in patients treated with alemtuzumab
Abstract
Background
Alemtuzumab has proven to be an effective treatment for patients with highly active multiple sclerosis (MS). However, its use has been limited by adverse events (AEs) as secondary autoimmunity, being the most frequent those involving the thyroid gland, observed in around 40% of patients.
Objectives
To explore whether patient blood lymphocyte profile before alemtuzumab treatment initiation can identify patients with an increased risk of developing later autoimmunity.
Methods
A multicentre prospective longitudinal study was performed, including fifty‐four Relapsing-Remitting MS (RRMS) patients diagnosed in five Spanish hospitals. Patient blood samples were collected before initiating treatment with alemtuzumab. Autoimmune AEs were defined as the development, at any point within 2 years of follow-up, of any autoimmune thyroid-associated event, immune thrombocytopenia and/or autoimmune nephropathy. Differences were assessed using Man-Whitney U tests. Cut-off values were established using ROC curves to predict autoimmune AEs. Odds ratios were calculated by Fisher tests.
Results
Fifty‐four RRMS patients, 36 (66.7%) women, with a median (range) age of 28 (13–67) years and median (range) follow-up of 6 (0-20) years. Fourteen patients (25.9%) experienced autoimmune AEs, and all of them were dysthyroidism. No immune thrombocytopenia or nephropathies were observed. No statistical differences were found in clinical and demographic characteristics between patients who developed autoimmune AEs and those who did not. Patients who experienced autoimmune AEs before treatment onset had a higher percentage of blood CD19+ B cells (p=0.001), with a higher relative percentage of naïve B cells and plasmablasts. When explored total cell numbers, only plasmablast levels remained significant (p=0.02). A lower risk of autoimmune AEs after alemtuzumab was observed among patients with less than 7.6% of blood CD19+ B cells [odds ratio (OR) 16, confidence interval (CI) 3.86–58.95, p<0.0001] or less than 0.13% of plasmablast cells [OR 9.33, CI 2.17–42.65, p=0.002].
Conclusions
A low percentages of blood CD19+ B cells or plasmablasts before Alemtuzumab treatment predicted a lower risk of autoimmune AEs.
Author Of 8 Presentations
LB1168 - COVID-19 in MS patients: susceptibility and severity risk factors (ID 1524)
Abstract
Background
In the present pandemic, gathering information regarding Multiple Sclerosis (MS) patients with COVID-19 is needed.
Objectives
To investigate the incidence of COVID-19 in a Barcelona cohort of MS patients, to describe the characteristics of MS patients with COVID-19, and to identify risk factors for susceptibility and severity.
Methods
Retrospective cohort study of adult MS patients included from February to May 2020. COVID-19 and non-affected cases were identified through a COVID-19 mail survey and clinical visits. Demographic, clinical, MS characteristics, and laboratory data (lymphocyte and CD19+ count, immunoglobulins, and vitamin D) were obtained. Serological SARS-CoV-2 testing was performed in all suspected cases. We examined the relationship between the previously mentioned variables with COVID-19 susceptibility and severity.
Results
Out of the 2903 surveys sent, a total of 875 were answered. 117 (13.37%) patients were excluded for not meeting inclusion criteria. 48 out of 758 were suspected COVID-19 and the remaining were classified as non-COVID-19. The estimated incidence was 6.3%. 45 additional suspected COVID-19 cases were detected in clinical visits. In the multivariate analysis, COVID-19 susceptibility was associated with being younger (OR 0.54, IC95% 0.34-0.87,p<0.01), having had contact with a confirmed case (OR 193.20, IC95% 55.34-674.43,p<0.01), living in Barcelona (OR 2.35, IC95% 1.08-5.09, p=0.03) and a longer MS disease duration (OR 1.43, IC95% 1.10-1.85,p<0.01). In patients treated with an anti-CD20 therapy, COVID-19 susceptibility increased with treatment duration (OR 3.36, IC95% 1.42-7.96, p<0.01). 19 (20.43%) of the 93 COVID-19 cases were hospitalized, 9(9.68%) presented a severe course and 2(2.15%) of them died. In the univariate analysis, older patients with comorbidities, a progressive and longer MS duration, and without disease-modifying therapies, presented a more severe disease although these results were not observed in the multivariate analysis. Out of the 79 (84.9%) with serological test, 45.6% had generated antibodies and 17.6% in patients receiving anti-CD20. No relation of lymphopenia, vitamin D, or immunoglobulins levels with COVID-19 susceptibility or severity was found.
Conclusions
MS patients present similar incidence, risk factors, and outcomes for COVID-19 than the general population. Patients treated with an anti-CD20 therapy for a longer period of time might be in a higher risk of COVID-19 and of generating lower antibody response.
LB1240 - A kappa free light chain index of 6.6 represents an alternative to positive oligoclonal bands in the 2017 McDonald criteria (ID 2125)
- G. Arrambide
- C. Espejo
- R. Dieli
- C. Auger
- M. Castillo
- M. Rodriguez-Barranco
- P. Carbonell-Mirabent
- J. Río
- J. Castilló
- A. Vidal-Jordana
- Í. Galán
- C. Nos
- M. Comabella
- B. Rodríguez-Acevedo
- L. Midaglia
- A. Zabalza
- A. Cobo Calvo
- P. Tagliani
- S. Cárdenas-Robledo
- J. Sastre-Garriga
- A. Rovira
- M. Hernández-González
- X. Montalban
- M. Tintore
Abstract
Background
Oligoclonal bands (OB) are part of the 2017 McDonald criteria but their determination is rater-dependent. Kappa free light chains (KFLC) are determined quantitatively and could be an alternative to OB, but a vendor-specific index cut-off is needed.
Objectives
To compare the proportion of patients with clinically isolated syndromes (CIS) and positive OB and a KFLC index equal or greater than 6.6 (KFLC-6.6, Leurs CE Mult Scler 2020) or 10.61 (KFLC-10.61, Gaetani L J Neuroimmunol 2020). To compare the diagnostic properties of OB, KFLC-6.6 and KFLC-10.61 for 2nd attack and 2017 MRI dissemination in space (DIS) and time (DIT).
Methods
MRIs were obtained 3-5 months after the CIS, at 1 year and every 5 years. OB were determined by isoelectric focusing combined with immunoblotting. We selected 228 patients with sufficient data to assess DIS and DIT, OB determination and enough remnant frozen samples to measure KFLC by turbidimetry (Optilite, The Binding Site). We compared the proportion of patients with positive OB, KFLC-6.6 and KFLC-10.61 and the 3-year diagnostic properties for the following outcomes: 2nd attack (n=179) and MRI DIS and DIT (n=192).
Results
Of all patients, 146 (64.0%) had OB, 147 (65.5%) KFLC-6.6 and 137 (60.1%) KFLC-10.61. In total, 130 (57.0%) had OB and KFLC-6.6, 16 (7.0%) only OB, 17 (7.5%) only KFLC-6.6 and 65 (28.5%) had neither. As for OB and KFLC-10.61, 122 (53.5%) had both, 24 (10.5%) only OB, 15 (6.6%) only KFLC-10.61 and 67 (29.4%) had neither. At baseline, the criteria were fulfilled by patients with OB, KFLC-6.6 and KFLC-10.61 as follows: DIS 109/135 (80.7%), 114 (84.4%) and 106 (78.5%); DIT 70/87 (80.5%), 78 (89.7%) and 74 (85.1%); DIS plus DIT 64/78 (81.2), 71 (91.0%) and 67 (85.9); DIS plus OB 109 (100.0%), 101 (92.7%) and 94 (86.2); and McDonald 111/130 (85.4%), 113 (86.9%) and 106 (81.5%). The diagnostic properties of OB, KFLC-6.6 and KFLC-10.61 for 2nd attack were sensitivity 77.8, 85.6 and 78.0; specificity 44.9, 48.3 and 51.7; and accuracy 61.5, 67.0 and 65.4. Results for MRI DIS plus DIT were sensitivity 81.8, 87.9 and 82.6; specificity 66.7, 70.0 and 73.3; and accuracy 77.1, 82.3 and 79.7.
Conclusions
KFLC-10.61 had the greatest specificity and KFLC-6.6 the best overall diagnostic properties. The results were probably due to the higher proportion of positive KFLC patients with DIT compared to those with positive OB, suggesting KFLC-6.6 could be used as an alternative to OB in the McDonald criteria.
P0014 - Personalized and dynamic prognostic model from the Barcelona CIS cohot (ID 1607)
Abstract
Background
In the constantly evolving field of MS, personalized medicine is still one of the most important unmet need that requires further attention
Objectives
We aimed to develop a dynamic risk calculator to predict the long-term prognosis of MS in the context of a large MS Centre in Catalonia
Methods
This is an observational study based on data prospectively acquired from a deeply phenotyped CIS cohort from Barcelona. We first built a natural history baseline risk score (BRS) for predicting moderate disability, integrating baseline prognostic factors: Sex, age at CIS, CIS topography, number of T2 lesions, contrast-enhancing lesions (CEL) and oligoclonal bands. This BRS was designed as follows: For untreated patients, we built a Weibull model to estimate the median time to confirmed EDSS 3.0 and with these estimates we identified risk groups based on the median of the cut-offs of 2000 survival trees. Then we obtained the BRS of the full cohort. In patients with more than ten years of follow-up, we performed an inverse probability weighting to balance patients during their follow up for the propensity of being treated or lost to follow-up. The weights were estimated via a proportional hazards (PH) Cox model considering both baseline information (CIS year, BRS) and time-dependent (diagnosis status, new T2 lesions, CEL and cumulative number of relapses). Finally, a weighted PH Cox model was built to estimate the time to confirmed EDSS 3.0 considering the BRS and time-dependent events (new T2 lesions, cumulative number of relapses and first or second-line treatment use). Sensitivity analyses using other disability outcomes and different follow-ups were conducted.
Results
Of 956 patients, 577 (60.4%) were untreated before confirmed EDSS 3.0. Two BRS were obtained: low and high-BRS. Of 400 patients followed for more than ten years, 226 (56.5%) were low-BRS and 174 (43.5%) were high-BRS. High-BRS showed a HR=2.16 95%CI (1.16,4.02). Each new T2 lesion presented HR=1.04 95%CI (1.00,1.08) and each new relapse HR=1.46 95%CI (1.23,1.74). Being on second-line treatment showed a protective effect (HR=0.23 95%CI (0.06,0.94)) but no association was found for first-line treatments (HR=1.32 95%CI (0.67,2.60). Sensitivity analyses confirmed the association between BRS, new T2 lesions and the accumulation of relapses with the prognosis. However, treatment results were inconclusive.
Conclusions
Presenting a high-BRS doubles the risk of reaching moderate disability. Each new lesion and new relapse increses the risk by 4% and 46%, respectively; and second-line treatments seem to be protective. If validated, this risk calculator could be a crucial step to personalized medicine.
P0020 - A down-regulation of the type I interferon signaling pathway is associated with the response to teriflunomide in multiple sclerosis. (ID 1584)
Abstract
Background
Teriflunomide is an oral first-line treatment of patients with relapsing-remitting multiple sclerosis (RRMS) that has been shown to decrease clinical relapses, reduce brain magnetic resonance imaging (MRI) activity, and slow progression of disability. However, the drug exhibits only limited effectiveness and does not produce clinical benefits in a proportion of MS patients.
Objectives
We aimed to identify differentially expressed genes and cellular pathways associated with the responder and non-responder status in RRMS patients treated with teriflunomide by means of RNA sequencing (RNA-seq).
Methods
RRMS patients treated with teriflunomide were classified into those with No evidence of disease activity (NEDA 3) and those with EDA after 12 months of treatment. Eleven responders [8 females; mean age (standard deviation): 45.8 years (4.5)] and 10 non-responders [8 females; 41.8 years (10.3)] were included in the study. RNA-seq was performed in RNA samples isolated from peripheral blood mononuclear cells before and after 12 months of teriflunomide treatment. 100 bp, paired-end RNA sequencing was performed by using DNAseqTM Technology. Comparative analysis of differentially expressed genes between responders and non-responders was performed at baseline and after 12 months of treatment. Pathway analysis was based on KEGG database using statistically significant genes.
Results
Pathway analysis revealed the type I interferon (IFN) signaling pathway as the most significantly associated with the responder phenotype after 12 months of teriflunomide treatment (p<0.0001). In this context, expression levels for genes known to be predominantly or selectively induced by type I IFNs such as SP100, ZBP1, IFI27, ISG20, IFITM1, IFITM2, MX1, STAT1, PARP9, IFI35, RGS1, RSAD2, IFI44L, IRF1, DDX58, IFI6, IFIT1 and IFIT5 were significantly reduced by the effect of teriflunomide after 12 months of treatment in responders compared to non-responders. At baseline, expression levels for type I IFN genes were similar between responders and non-responders.
Conclusions
Type I IFNs are known to activate dendritic cells, enhance humoral immunity, and favor Th1 immune responses. A down-regulation of type I IFN genes after 12 months of treatment may explain the beneficial effect of teriflunomide in responders. Mechanistic studies are currently underway to investigate the functional implication of the type I interferon signaling pathway in the response to teriflunomide.
P0087 - Identification of proteins associated with ageing in patients with progressive multiple sclerosis (ID 1589)
Abstract
Background
Similar to other neurodegenerative disorders, the onset of progressive MS is related to age, a factor known to amplify neurodegeneration. Recent studies have shown that exposure of aged mice to a young blood circulation through parabiosis or administration of young blood plasma (plasma from 3-month-old mice) reverses cognitive deficits observed with normal ageing.
Objectives
We aimed to search for soluble factors in the serum of patients with progressive MS that are affected by age and are differentially decreased in patients compared to healthy controls (HC) of similar age.
Methods
Protein levels were determined in serum samples from a cohort of 30 untreated MS patients (15 patients with secondary progressive MS - SPMS - and 15 with primary progressive MS - PPMS) and 25 HC. Progressive MS patients were classified according to age and clinical characteristics into the following three groups (each group containing 10 patients, 5 with SPMS and 5 with PPMS): (i) 40 ± 3 years old, disease duration <10 years, EDSS <4.5; (ii) 50 ± 3 years old, disease duration between 10-20 years, EDSS between 4.5-6; and (iii) 60 ± 3 years old, disease duration >20 years, EDSS >6.5. HC were classified based on age into the following groups (each group containing 5 individuals): 20, 30, 40, 50, and 60 ± 3 years old. To maximize the breadth and depth of serum proteome coverage, the top 70 abundant proteins in serum were depleted. Afterwards, samples were subjected to mass spectrometry.
Results
After depletion of the most abundant proteins in serum, a total of 2,059 molecules were detected in all 55 samples. The maSigPro package (R Bioconductor) was used to identify proteins with significantly divergent expression profiles as a function of time. A quadratic regression model was fit for each molecule and 823 proteins, among the 2059 analyzed, were found differentially expressed (FDR < 0.05) between the MS group and HC. The serum levels of the following proteins were significantly decreased by ageing in progressive MS patients compared with HC and were selected for further studies: PLXDC2, Neudesin, Myostatin, Myocilin, and EMMPRIN.
Conclusions
Protein expression profiling associated with ageing in progressive MS patients and HC lead to the identification of number of promising candidates associated with neurotrophic functions, myelination, and nervous system development. Results obtained by mass spectrometry need to be validated by targeted immunoassays.
P0330 - Effects of cladribine on proliferation, survival and cytokine release of human astrocytes (ID 1581)
Abstract
Background
Cladribine is a synthetic purine nucleoside analogue with immunosuppressive functions that has demonstrated beneficial effects in patients with relapsing-remitting multiple sclerosis (MS) and that may also regulate the immune function as an analogue of adenosine receptors. Although the effect of cladribine is well studied on immune cells, it remains unveiled how it affects the immune function of glial populations of the central nervous system.
Objectives
In the context of MS, we aimed to test the effect of cladribine on proliferation, survival and cytokine release of human astrocytes.
Methods
To assess the effect of cladribine on cell survival and proliferation, primary human astrocytes were cultured with cladribine at high concentrations (2µM, 0.2µM), at the mean estimated brain exposure of the drug (0.02µM) and at a low concentration (0.002µM) for 72h. The percentages of dead and proliferating cells were determined by flow cytometry. To assess the effect of cladribine on cytokine release, human astrocytes were stimulated for 6h with 20ng/ml IL1-β and TNF-α. The stimulus was withdrawn and cells were cultured for additional 18h. Cladribine was added for the whole 24h of culture. Supernatants were harvested to quantify IL1-β, IL6, TNF-α and GM-CSF release by Luminex. To assess the effect of cladribine independently of deoxycytidine kinase (DCK), deoxycytidine was also added to human astrocytes.
Results
Only high concentrations of cladribine induced death on human astrocytes (2µM: 35.89%±7.62 or 0.2µM: 7.27%±3.12 vs control: 3.17%1.84±; p<0.0001 and p=0.156, respectively) and inhibited their proliferative capacity (2µM: 0.96%±1.14 or 0.2µM: 14.06%±5.44 vs control: 33.06%±1.42; both p-values<0.0001). Additionally, the percentage of proliferating cells in the 2µM and 0.2µM conditions presented a limited capacity of proliferation (measured as the Relative Intensity of Proliferation Staining respect to basal; 2µM: 0.24±0.04 and 0.2µM: 0.55±0.22, both p-values<0.0001). When DCK activity was blocked by deoxycytidine, cell death and proliferation were reversed to control condition values. We are currently determining the effect of cladribine on pro-inflammatory cytokine release by human astrocytes.
Conclusions
The mean estimated brain exposure to cladribine does not influence cell survival or proliferation of human astrocytes neither in a DCK-dependent nor in a DCK-independent manner, suggesting that cladribine does not affect the normal astrocyte function in MS patients.
P0975 - Lipid-specific oligoclonal IgM bands condition age-related changes in multiple sclerosis (ID 1396)
- C. Picón
- A. Tejeda-Velarde
- J. Fernandez-Velasco
- M. Comabella
- R. Alvarez-Lafuente
- E. Quintana
- S. Sainz de la Maza
- E. Monreal
- N. Villarrubia
- J. Álvarez-Cermeño
- M. Domínguez-Mozo
- L. Ramió I Torrentà
- E. Rodríguez-Martin
- E. Roldán
- Y. Aladro
- S. Medina
- M. Espiño
- J. Masjuan
- C. Matute-Blanch
- M. Muñoz-San Martin
- C. Espejo
- C. Guaza
- L. Costa-Frossard
- L. Villar
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.
P1119 - Disease activity in patients with multiple sclerosis treated with alemtuzumab due to a pregnancy desire (ID 1511)
Abstract
Background
Counselling and managing women with active Multiple Sclerosis (MS) during pregnancy and the postpartum period is a challenge. Alemtuzumab (ALZ) might be an option for patients with severe MS who desire pregnancy. However, data on relapse activity during and after pregnancy is scarce.
Objectives
Our objective was to describe our experience with ALZ treatment prescribed in highly active MS women with a pregnancy desire.
Methods
From all ALZ treated women (n=62), patients starting treatment because of a pregnancy desire were selected. Demographic, clinical, and radiological data before and during ALZ treatment as well as during and after pregnancy were collected.
Results
From 1st September 2019, thirteen patients were identified with a mean age at ALZ onset of 33.9 years (SD 5.5), median disease duration of 12.0 years (IQR 12.5). The median number of relapses 1 year prior to ALZ onset was 2.0 (IQR 2.0) and 6 out of 10 patients (60%) had Gd-enhancing lesions at baseline MRI (median of 4.5 lesions; IQR 8.3). Only one patient was treatment naïve prior to ALZ onset, 5 patients (38%) were receiving fingolimod, 3 patients (23.1%) injectable therapies, and 3 patients (23,1%) other monoclonal antibodies. As of 1st June 2020, 4 patients (30%) were still not pregnant, 8 patients (61.5%) have had a full-term pregnancy, and 1 patient (7.7%) was still pregnant. All 9 pregnant patients have received two cycles of ALZ with a median time from the last ALZ dose to pregnancy of 9 months (IQR 18). After 1-2 years ALZ treatment, and prior to the pregnancy, 4 out of 9 patients (44.4%) had at least one relapse and 3 (33.3%) patients had an active brain MRI either at 12 or 24 months after ALZ onset. During pregnancy, only 1 patient had a relapse during the first trimester. During the postpartum period, 2 out of 8 (25%) patients experienced a disease reactivation with a relapse occurring with a mean time of 42 days (SD 41) after delivery and a brain MRI showing a high number of Gd-enhancing lesions.
Conclusions
Alemtuzumab treatment in women with high disease activity and a pregnancy desire might be an option. However, it is warned that some patients could present a disease reactivation short after delivery. Thus, close monitoring is needed, especially in patients with a high disease activity during the preconception period.