Concurrent administration of serotonergic antidepressants and ozanimod in participants with relapsing multiple sclerosis from the open-label extension DAYBREAK trial.

Background: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro.

Objective: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.

Attack adjudication in neuromyelitis optica spectrum disorder: Substantiation of criteria by magnetic resonance imaging and biomarkers in N-MOmentum.

Background: The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD).

Objective: Evaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum.

Methods: Adults ( = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo.

Effects of baseline age and disease duration on the efficacy and safety of siponimod in patients with active SPMS: Post hoc analyses from the EXPAND study.

Background: Older age and longer disease duration (DD) may impact the effectiveness of disease-modifying therapies in patients with multiple sclerosis (MS). Siponimod is a sphingosine 1-phosphate receptor modulator approved for the treatment of active secondary progressive MS (SPMS) in many countries. The pivotal phase 3 EXPAND study examined siponimod versus placebo in a broad SPMS population with both active and non-active disease.

A Predictive Autoantibody Signature in Multiple Sclerosis.

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. Here, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster of PwMS that share an autoantibody signature against a common motif that has similarity with many human pathogens.

Association of daily physical activity with brain volumes and cervical spinal cord areas in multiple sclerosis.

Background: Remote activity monitoring has the potential to evaluate real-world, motor function, and disability at home. The relationships of daily physical activity with spinal cord white matter and gray matter (GM) areas, multiple sclerosis (MS) disability and leg function, are unknown.

Objective: Evaluate the association of structural central nervous system pathology with ambulatory disability.

Immune cell subset profiling in multiple sclerosis after fingolimod initiation and continued treatment: The FLUENT study.

Background: Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood.

Objective: Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes.

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial.

Background: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS.

Objective: To characterize long-term safety and efficacy of ozanimod.

Methods: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.

Long-term efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis: Analysis of EXPAND core and extension data up to >5 years.

Background: Siponimod significantly reduced the risk of confirmed disability progression (CDP), worsening in cognitive processing speed (CPS), relapses, and magnetic resonance imaging (MRI) measures of brain atrophy and inflammation versus placebo in secondary progressive multiple sclerosis (SPMS) patients in the Phase 3 EXPAND study.

Objective: The aim of this study was to assess long-term efficacy and safety of siponimod 2 mg/day from the EXPAND study including the extension part, up to > 5 years.

Methods: In the open-label extension part, participants receiving placebo during the core part were switched to siponimod (placebo-siponimod group) and those on siponimod continued the same treatment (continuous siponimod group).

Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial.

Background: Magnetic resonance imaging (MRI) measurements of gray matter (GM) atrophy and magnetization transfer ratio (MTR; correlate of myelination) may provide better insights than conventional MRI regarding brain tissue integrity/myelination in multiple sclerosis (MS).

Objective: To examine the effect of siponimod in the EXPAND trial on whole-brain and GM atrophy, newly formed normalized magnetization transfer ratio (nMTR) lesions, and nMTR-assessed integrity of normal-appearing brain tissue (NABT), cortical GM (cGM), and normal-appearing white matter (NAWM).

Methods: Patients with secondary progressive multiple sclerosis (SPMS) received siponimod (2 mg/day;  =1037) or placebo ( = 523).

Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study.

Background: The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions.

Objective And Methods: This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24.

Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis.

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI).

Objective And Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.

Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD.

Background: In the N-MOmentum trial, the risk of an adjudicated neuromyelitis optica spectrum disorder (NMOSD) attack was significantly reduced with inebilizumab compared with placebo.

Objective: To demonstrate the robustness of this finding, using pre-specified sensitivity and subgroup analyses.

Methods: N-MOmentum is a prospective, randomized, placebo-controlled, double-masked trial of inebilizumab, an anti-CD19 monoclonal B-cell-depleting antibody, in patients with NMOSD.

Siponimod: Disentangling disability and relapses in secondary progressive multiple sclerosis.

Background: In multiple sclerosis, impact of treatment on disability progression can be confounded if treatment also reduces relapses.

Objective: To distinguish siponimod's direct effects on disability progression from those on relapses in the EXPAND phase 3 trial.

Methods: Three estimands, one based on principal stratum and two on hypothetical scenarios (no relapses, or equal relapses in both treatment arms), were defined to determine the extent to which siponimod's effects on 3- and 6-month confirmed disability progression were independent of on-study relapses.

Validation of a consumer-grade activity monitor for continuous daily activity monitoring in individuals with multiple sclerosis.

Background: Technological advancements of remote-monitoring used in clinical-care and research require validation of model updates.

Objectives: To compare the output of a newer consumer-grade accelerometer to a previous model in people with multiple sclerosis (MS) and to the ActiGraph, a waist-worn device widely used in MS research.

Methods: Thirty-one individuals with MS participated in a 7-day validation by the Fitbit Flex (Flex), Fitbit Flex-2 (Flex2) and ActiGraph GT3X.

Longitudinally persistent cerebrospinal fluid B cells can resist treatment in multiple sclerosis.

B cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B cells exist in the cerebrospinal fluid (CSF), meninges, and CNS parenchyma of MS patients. We sought to investigate the presence of clonally related B cells over time by performing Ig heavy chain variable region repertoire sequencing on B cells from longitudinally collected blood and CSF samples of MS patients (n = 10).

Toward a low-cost, in-home, telemedicine-enabled assessment of disability in multiple sclerosis.

Background: Remote assessment of neurological disability in people with multiple sclerosis (MS) could improve access to clinical care and efficiency of clinical research.

Objective: To develop and validate a telemedicine-based MS disability examination that does not require an in-home examiner.

Methods: Adults with MS were recruited after a standardized in-person Expanded Disability Status Scale (EDSS) evaluation, and within 1 week underwent a blinded televideo-enabled EDSS examination with a different clinician.

Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study.

Background: Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5.

Objective: Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis.

Methods: In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.

Harnessing electronic medical records to advance research on multiple sclerosis.

Background: Electronic medical records (EMR) data are increasingly used in research, but no studies have yet evaluated similarity between EMR and research-quality data and between characteristics of an EMR multiple sclerosis (MS) population and known natural MS history.

Objectives: To (1) identify MS patients in an EMR system and extract clinical data, (2) compare EMR-extracted data with gold-standard research data, and (3) compare EMR MS population characteristics to expected MS natural history.

Methods: Algorithms were implemented to identify MS patients from the University of California San Francisco EMR, de-identify the data and extract clinical variables.

Clonal relationships of CSF B cells in treatment-naive multiple sclerosis patients.

A role of B cells in multiple sclerosis (MS) is well established, but there is limited understanding of their involvement during active disease. Here, we examined cerebrospinal fluid (CSF) and peripheral blood (PB) B cells in treatment-naive patients with MS or high-risk clinically isolated syndrome. Using flow cytometry, we found increased CSF lymphocytes with a disproportionate increase of B cells compared with T cells in patients with gadolinium-enhancing (Gd+) lesions on brain MRI.