Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.

Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods.

Delay from treatment start to full effect of immunotherapies for multiple sclerosis.

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events.

Early clinical markers of aggressive multiple sclerosis.

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype.

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder.

Background: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.

ABO blood group distributions in multiple sclerosis patients from Basque Country; O as a protective factor.

Background: The relation between ABO/Rh groups and multiple sclerosis (MS) has been proposed in several studies, however there is a controversy about the role of these groups in the disease. Although it has been reported that some groups can be protective or risk factors, there is no consensus and discordant reports can be found in the literature.

Objectives And Methodology: In this short report, we analyze the ABO/Rh distribution in a MS cohort of 265 patients and compare these frequencies with the results obtained from the Basque Blood Donors bank (17,796 individuals) of the same region.

Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype.

Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups.

Objective: We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets.

Risk of secondary progressive multiple sclerosis: A longitudinal study.

Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.

Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.

Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort.

Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study.

Background: Exposure to disease-modifying therapy (DMT) during early pregnancy in women with relapsing-remitting MS (RRMS) may be increasing.

Objective: To retrospectively determine incidence of pregnancy, DMT exposure and pregnancy outcomes in women with RRMS.

Methods: We identified all women with RRMS aged 15-45 years in the MSBase Registry between 2005-2016.

The First Dose of Fingolimod Affects Circulating Extracellular Vesicles in Multiple Sclerosis Patients.

Extracellular vesicles (EVs) are membrane-bound particles involved in intercellular communication. They carry proteins, lipids, and nucleotides such as microRNAs (miRNAs) from the secreting cell that can modulate target cells. We and others have previously described the presence of EVs in peripheral blood of multiple sclerosis (MS) patients and postulated them as novel biomarkers.

Different clinical response to interferon beta and glatiramer acetate related to the presence of oligoclonal IgM bands in CSF in multiple sclerosis patients.

Objective: To study the efficacy of interferon beta (IFNβ) and glatiramer acetate (GA) related to the presence of oligoclonal M bands (OCMB) in the cerebrospinal fluid in relapsing-remitting multiple sclerosis (RRMS).

Method: This is an observational, multicenter and retrospective study with prospectively collected data of patients that started treatment with IFNβ or GA. Treatment decision was made blinded to the OCMB status.

Lymphocyte count in peripheral blood is not associated with the level of clinical response to treatment with fingolimod.

Background: Fingolimod is an efficient and safe drug for treating relapsing-remitting multiple sclerosis (RRMS). In vivo, fingolimod is phosphorylated and binds to "sphingosine-1-phosphate"(S1P) receptors that are expressed in a wide range of cells, including lymphocytes. Under the effect of fingolimod, lymphocytes are retained in lymphoid tissues through the regulation of S1P receptors.

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms.

Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis.

Multiple sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g.

Progressive changes in non-coding RNA profile in leucocytes with age.

It has been observed that immune cell deterioration occurs in the elderly, as well as a chronic low-grade inflammation called inflammaging. These cellular changes must be driven by numerous changes in gene expression and in fact, both protein-coding and non-coding RNA expression alterations have been observed in peripheral blood mononuclear cells from elder people. In the present work we have studied the expression of small non-coding RNA (microRNA and small nucleolar RNA -snoRNA-) from healthy individuals from 24 to 79 years old.

Bilateral Retrobulbar Optic Neuropathy Associated With Golimumab.

We report the first documented case of retrobulbar optic neuropathy associated with golimumab. A 48-year-old man was admitted with a 3-week history of progressive visual loss of his left eye. He had received a second infusion of golimumab for ankylosing spondylitis 10 days before admission.

Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

Background: Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years.

Methods: In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts.

Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis.

Objective: To evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy.

Methods: The epochs between Expanded Disability Status Scale (EDSS) steps 3-6, 4-6 and 6-6.5 were analysed.

Defining secondary progressive multiple sclerosis.

A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies.

Predictors of long-term disability accrual in relapse-onset multiple sclerosis.

Objective: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis.

Methods: Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter.

Neuromyelitis optica spectrum disorders: Comparison according to the phenotype and serostatus.

Objective: To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO.

Methods: This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays.

Contribution of different relapse phenotypes to disability in multiple sclerosis.

Objective: This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis.

Methods: Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores).

SncRNA (microRNA &snoRNA) opposite expression pattern found in multiple sclerosis relapse and remission is sex dependent.

Multiple sclerosis (MS) is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes of neurological disability (relapses) followed by a recovery phase (remission).

Age gene expression and coexpression progressive signatures in peripheral blood leukocytes.

Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network.