73 research outputs found
Rituximab suppresses disease activity after natalizumab withdrawal: an exploratory study
Background Natalizumab is highly effective in reducing multiple sclerosis disease activity; however it carries a risk of progressive multifocal leukoencephalopathy, that represents the main reason of drug discontinuation. After natalizumab withdrawal, reactivation of disease is soon observed and, until now, it is not known which treatment strategy should be followed after natalizumab discontinuation. Aim of this study is to evaluate rituximab efficacy in controlling disease activity after natalizumab withdrawal
Successful pregnancy and disease outcomes in a NMOSD patient treated with tocilizumab
Abstract Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune relapsing disease involving the central nervous system with predominant inflammatory attack of optic nerves, spinal cord and area postrema, often leading to severe disability. Women with NMOSD typically experience adverse pregnancy outcomes and high relapse rates during pregnancy and the postpartum period. Case report Herein we present a case of pregnancy in a young NMOSD woman treated with tocilizumab. The course of her pregnancy was clinically unremarkable and treatment whit Tocilizumab was well tolerated. Conclusions This case raises the possibility that the modulation of immune system by inhibitors of the IL-6 pathway could a promising therapeutic option for pregnancy in NMOSD patient
The use of the 25 Sprotte needle markedly reduces post-dural puncture headache in routine neurological practice
Neutralizing antibodies against IFNâβ in multiple sclerosis: antagonization of IFNâβ mediated suppression of MMPs
Neutralizing antibodies (NAb) against interferonâβ (IFNâβ) develop in about a third of treated multiple sclerosis patients and are believed to reduce therapeutic efficacy of IFNâβ on clinical and MRI measures. The expression of the interferon acuteâresponse protein, myxovirus resistance protein A (MxA) is a sensitive measure of the biological activity of therapeutically applied IFNâβ and of its reduced bioavailability due to NAb. However, MxA may not be operative in the pathogenesis of multiple sclerosis or the therapeutic effect of IFNâβ. Instead, matrix metalloproteinases (MMPs) are increased in brain tissue, CSF and blood circulation of multiple sclerosis patients and function as effector molecules in several steps of multiple sclerosis pathogenesis. One of the molecular mechanisms by which IFNâβ exerts its beneficial effect in multiple sclerosis is reduction of MMPâ9 expression and increase of its endogenous tissue inhibitor, TIMPâ1. Quantitative PCR measurements of MMPâ2 and MMPâ9, TIMPâ1 and TIMPâ2, and MxA were performed in peripheral mononuclear cells from clinically stable multiple sclerosis patients with relapsing remitting disease course after shortâterm and longâterm treatment with IFNâβ. IFNâβ therapy downâregulated the expression of MMPâ9 and abolished that of MMPâ2 in longâterm, but not shortâterm treated multiple sclerosis, while levels of MxA were increased in both instances. The presence of NAb reversed these effects, i.e. led to reduced MxA and increased MMPâ2/MMPâ9 expression levels compared with NAb- patients. In contrast, expression of TIMPs in peripheral blood mononuclear cells remained unaffected by IFNâβ therapy and the presence of NAb. While MxA is able to detect the biological action and reduced bioavailability of IFNâβ on the basis of single injections, only MMPâ9 shows quantitative correlation with the NAb titre. Together with evidence that an imbalance between MMP and TIMP expression is a crucial pathogenetic feature in multiple sclerosis, these findings support the concept of a significant role of NAb in reducing the therapeutic efficacy of IFNâ
Learning from Nature: Pregnancy Changes the Expression of Inflammation-Related Genes in Patients with Multiple Sclerosis
Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood
Risk of Getting COVID-19 in People With Multiple Sclerosis
Background and Objectives
Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in
people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies
(DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection
has not been evaluated so far. The objective of this study was to assess risk factors of contracting
SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR).
Methods
Acase-control (1:2) studywas set up. Cases included PwMSwith a confirmed diagnosis ofCOVID-19,
and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity
scoreâmatched by the date of COVID-19 diagnosis, the date of last visit, and the region of
residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable
logistic regression models including demographic and clinical covariates. The impact of DMTs
was assessed in 3 independent logistic regression models including one of the following covariates: last
administeredDMT, previousDMTsequences, or the place where the last treatment was administered.
Results
A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without
COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly
associated (p < 0.02)with a higher risk of contractingCOVID-19. Patients receiving natalizumab as last
DMT(OR[95%CI]: 2.38 [1.66â3.42], p < 0.0001) and those who underwent an escalation treatment
strategy (1.57 [1.16â2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring
hospital access (1.65 [1.34â2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home.
Discussion
This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently
female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the
hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS.
Classification of Evidence
This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more
comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were
associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course
was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an
interferon beta agent was protective
SARS-CoV-2 vaccination and multiple sclerosis: a large multicentric study on relapse risk after the third booster dose
Background: COVID-19 vaccines have been recommended to people with multiple sclerosis (pwMS) and, to ensure durable immunity, a third booster dose has been administered in several countries. Data about potential risks associated with the third booster dose in pwMS, such as vaccine-triggered disease exacerbations, are still scarce. Objective: To investigate whether the administration of a third booster dose of mRNA COVID-19 vaccines was associated with an increased risk of short-term disease reactivation in a large cohort of pwMS. Methods: We retrospectively selected 1265 pwMS who received a third booster dose of an mRNA COVID-19 vaccine. Demographic and clinical data were collected, including the presence, number and characteristics of relapses in the 60 days prior to and after the third booster dose. Results: In the selected cohort, the relapse rate in the two months after administration of the third booster dose of mRNA COVID-19 vaccines did not increase when compared with the prior two months. Indeed, the percentage of pwMS experiencing relapses in the 60 days following the administration of the third booster dose was 2.1%, similar to the percentage recorded in 60 days prior to vaccination, which was 1.9%. Conclusions: The third booster dose of mRNA COVID-19 vaccines appeared to be safe for pwMS
Peripheral blood biomarkers in multiple sclerosis.
Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc
Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis
Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS).
Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.
Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses.
Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists
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