Target trial emulation to replicate randomised clinical trials using registry data in multiple sclerosis.

Unlabelled: BackgroundTarget trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity must be evaluated in each research domain by replicating randomised clinical trials (RCTs). We aimed to replicate eight RCTs evaluating the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS) using French registry data.

Methods: This multicentre, retrospective, observational study was conducted using data extracted in December 2023 from the (OFSEP) database.

Outcomes After Reversible Cerebral Vasoconstriction Syndrome With Convexity Subarachnoid Hemorrhage: Individual Patient Data Analysis.

Background And Objectives: The most common cause of convexity subarachnoid hemorrhage (cSAH) in younger patients (younger than 60 years) is reversible cerebral vasoconstriction syndrome (RCVS). Evidence on the long-term outcomes of future vascular events and functional outcome after cSAH due to RCVS is limited. We aimed to assess the rates and baseline predictors of our primary outcomes (cSAH, intracerebral hemorrhage (ICH), and ischemic stroke), functional outcome, and mortality after cSAH attributed to RCVS.

Durable B-Cell Impairment While Sparing IgA B Cells After Ocrelizumab Therapy in Multiple Sclerosis.

Objectives: Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, is highly efficient in relapsing-remitting multiple sclerosis (RR-MS). We assessed early cellular B-cell profiles in patients prior to OCR treatment, on OCR treatment, and after 15 months of therapy discontinuation. This study aims to provide new clues about the mechanisms of action of OCR and about disease pathophysiology.

Therapeutic Management During Pregnancy and Relapse Risk in Women With Multiple Sclerosis.

Importance: In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk.

Objective: To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies.

Design, Setting, And Participants: This was a multicenter retrospective cohort study using data from January 1990 to December 2023.

Sex-Related Gap in the Use of Disease-Modifying Therapies in Multiple Sclerosis.

Background And Objectives: In women with multiple sclerosis (MS), the therapeutic strategy may be influenced by the anticipation of future pregnancies, leading to underexposure to disease-modifying therapies (DMTs) and highly effective DMTs (HEDMTs) compared with men. We aimed to evaluate potential therapeutic inertia in women with MS and explore its causes.

Methods: We performed a retrospective cohort study based on data extracted on June 2023 from the Observatoire Français de la Sclérose en Plaques for all patients with a relapsing-remitting MS onset between 18 and 40 years.

Use of Disease-Modifying Therapies in Patients With Late-Onset Multiple Sclerosis.

Background And Objectives: The therapeutic strategy in patients with late-onset MS (LOMS) remains poorly defined. In this study, we aimed to evaluate both clinical and MRI outcomes between 2 cohorts of patients with relapsing-remitting LOMS treated or not yet treated.

Methods: Patients with relapsing-remitting MS were included for the analysis if disease onset occurred after 55 years and if they had at least one follow-up visit.

Secondary progression activity monitoring in MS despite an early highly active treatment the SPAM study.

Background: Real-world data suggest that the early use of highly active therapies (HAT) may reduce the risk of transition to secondary progressive MS (SPMS). However, current knowledge about predictive factors of outcomes needs to be improved. The primary objective of this study was to determine factors associated with the occurrence of SPMS in patients treated early after MS onset with an HAT.

Limited added value of systematic spinal cord MRI vs brain MRI alone to classify patients with MS as active or inactive during follow-up.

Background: The utility of systematic spinal cord (SC) MRI for monitoring disease activity after a multiple sclerosis (MS) diagnosis remains a topic of debate.

Objectives: To evaluate the frequency of disease activity when considering brain MRI alone versus both brain and SC MRI and to identify factors associated with the occurrence of new SC lesions.

Methods: We conducted a retrospective analysis of clinical and imaging data prospectively collected over 5 years as part of the EMISEP cohort study.

European experience of cladribine tablets in elderly patients with multiple sclerosis: Could it be the last treatment?

Background: Recent studies support the need for early and intensive disease-modifying treatment (DMT) for patients with multiple sclerosis (PWMS). Abrupt DMT withdrawal may risk disease reactivation. Recent studies showed that MS disease activity was not rare after DMT withdrawal for PWMS aged >45/55 y.

Pregnancy and birth outcomes in women with multiple sclerosis: Comparison of the RESPONSE study to the general French population.

Background: Retrospective studies did not show strong evidence of higher risk of adverse neonatal or pregnancy outcomes in women with multiple sclerosis (MS) compared to general population, but there are contradictory data on prematurity, cesarean section, and small birthweight for gestational age (SGA).

Methods: We compared pregnancy and birth outcomes in MS women included in RESPONSE, a French prospective cohort, with a recent survey (Enquête Nationale Périnatale (ENP)) describing leading indicators in perinatal epidemiology in France.

Results: On 7 April 2023, 476 pregnancies (461 MS women, 482 expected newborns) from RESPONSE were available.

Abnormal Brain MRI in Anti-NMDA Receptor Encephalitis: Clinical and Prognostic Implications.

Background And Objectives: Abnormal brain MRI is associated with poor outcomes in anti-N-methyl-d-aspartate receptor encephalitis (NMDARE). We aimed to characterize the lesions on brain MRI in NMDARE and to assess the clinical and prognostic associations.

Methods: This retrospective cohort study included patients with NMDARE identified at the French Reference Center for Autoimmune Encephalitis, with at least a one-year follow-up, and with available brain MRI results.

LymphoTEC: a Retrospective Real-World Study on Lymphocyte Reconstitution After Lymphopenia in Patients with Multiple Sclerosis Treated with Dimethyl Fumarate in France.

Introduction: Dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Some patients may develop lymphopenia on DMF; therefore, LymphoTEC evaluated absolute lymphocyte count (ALC) reconstitution after DMF discontinuation.

Methods: LymphoTEC was a retrospective, multicenter study of patients with RRMS in the Observatoire Français de la Sclérose en Plaques registry.

Assessing the Risk of Relapse After In Vitro Fertilization in Women With Multiple Sclerosis.

Background And Objectives: Older studies reported an increased risk of relapse after in vitro fertilization (IVF) in women with multiple sclerosis (MS), which has not been confirmed by more recent works. All these studies had several limitations, such as small sample sizes, absence of a control population, or lack of neurologic validation of the relapses. The aim of this study was to determine the risk of relapse after IVF in women with MS.

Disease-modifying treatment and disability progression in subclasses of patients with primary progressive MS: results from the Big MS Data Network.

Background: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.

TWEAK and TNFɑ Pro-inflammatory Soluble Cytokines and their Specific Autoantibodies Secretion in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a complex, chronic inflammatory disease of the central nervous system, where immune dysregulation plays a critical role. We sought to explore the modulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFɑ) and TNF-like weak inducer of apoptosis (TWEAK), along with their respective autoantibodies, TNAb and TWAb, and to decipher potential associations between these and clinical characteristics which could assist personalized therapy in MS. We also assessed the complementarity to leading candidate biomarkers in MS patient monitoring, namely, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL).

Association between education level and access to disease-modifying treatment in patients with multiple sclerosis in France.

Background: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS).

Objective: This study aimed to analyze the association between education level and DMT use in France.

Methods: All patients from OFSEP network with MS onset over 1996-2014 and aged ⩾ 25 years at onset were included.

Association between education level and disability progression in patients with multiple sclerosis in France.

Background: Studies have reported an association between socioeconomic status and disability progression in multiple sclerosis (MS), but findings using the pre-MS individual socioeconomic status are missing.

Objective: The objective was to investigate the association between education level and disability progression.

Methods: All Observatoire Français de la Sclérose en Plaques (OFSEP) patients with MS clinical onset over 1960-2014, and aged ⩾25 years at MS onset were included.

TEC-ADHERE: Real-World Persistence and Adherence on Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis in the French OroSEP Patient-Support Program.

Introduction: Treatment persistence and adherence are essential for achieving therapeutic goals in patients with multiple sclerosis (MS). OroSEP is an independent patient-support program (PSP) in France for patients with relapsing-remitting MS (RRMS) receiving oral disease-modifying therapies.

Methods: TEC-ADHERE (NCT04221191; 08/19/2019-09/15/2022) was a prospective, non-interventional, phase 4 study to assess the effect of OroSEP on persistence and adherence to dimethyl fumarate (DMF; Tecfidera™) in patients with RRMS.

Choroid plexus enlargement correlates with periventricular pathology but not with disease activity in radiologically isolated syndrome.

Background: Choroid plexus (ChP) enlargement is an emerging radiological biomarker in multiple sclerosis (MS).

Objectives: This study aims to assess ChP volume in a large cohort of patients with radiologically isolated syndrome (RIS) versus healthy controls (HC) and explore its relationship with other brain volumes, disease activity, and biological markers.

Methods: RIS individuals were included retrospectively and compared with HC.

Serum NfL and GFAP are weak predictors of long-term multiple sclerosis prognosis: A 6-year follow-up.

Background: Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising biomarkers that might be associated with clinical and radiological markers of multiple sclerosis (MS) severity. However, it is not known whether they can accurately identify patients at risk of disability progression in the medium and long term.

Objectives: We wanted to determine the association between sNfL and sGFAP, Expanded Disability Status Scale score changes, and conversion to secondary progressive MS (SPMS) in a cohort of 133 patients with relapsing remitting MS.

Loss of heterozygosity in CCM2 cDNA revealing a structural variant causing multiple cerebral cavernous malformations.

Loss-of-function variants in CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10 genes are identified in the vast majority of familial cases with multiple cerebral cavernous malformations. However, genomic DNA sequencing combined with large rearrangement screening fails to detect a pathogenic variant in 5% of the patients. We report a family with two affected members harboring multiple CCM lesions, one with severe hemorrhages and one asymptomatic.