Publications by authors named "Robert Bermel"

Background And Objectives: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS).

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Background: A digital adaptation of the nine-hole peg test (9HPT) was developed with the potential to provide novel disability features for patients with multiple sclerosis (PwMS).

Objectives: The objectives were to evaluate the 9HPT features based on reliability, prognosis, and discrimination between treatment groups.

Methods: The MS partners Advancing Technology and Health Solutions (MS PATHS) cohort data were used to derive new features including completion time and speed.

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Objective: Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825).

Methods: Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.

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Article Synopsis
  • - Patients with multiple sclerosis (PwMS) face a higher risk of infections, especially those treated with ocrelizumab (OCR), as shown in a study involving 6,155 patients over a median period of 3.7 years.
  • - Serious infections (SIs) were reported at an incidence rate of 1.50 per 100 patient years for relapsing MS and 3.70 for progressive MS, with lower respiratory, urinary, abdominal, gastrointestinal, and skin infections being the most common.
  • - Significant risk factors for SIs included comorbidities, recent relapses, and higher disability scores, particularly in patients with progressive MS where a high EDSS score indicated a fourfold increase in
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Background: The long-term disease trajectory of people living with multiple sclerosis (MS) can be improved by initiating efficacious treatment early. More quantitative evidence is needed on factors that affect a patient's risk of disability worsening or possibility of improvement to inform timely treatment decisions.

Methods: We developed a multistate model to quantify the influence of demographic, clinical, and imaging factors on disability worsening and disability improvement simultaneously across the disability spectrum as measured by the Expanded Disability Status Scale (EDSS).

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Introduction: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). The safety profile and patient preference for conventional versus shorter ocrelizumab infusions were investigated in the ENSEMBLE PLUS study.

Methods: ENSEMBLE PLUS was a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810), comparing outcomes in patients with early-stage relapsing-remitting MS receiving ocrelizumab 600 mg over the approved 3.

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Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation.

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Objectives: We evaluate the potential clinical and cost impacts of discontinuing disease-modifying therapy (DMT) in people with multiple sclerosis (PwMS) when age-related immunosenescence can reduce DMT efficacy while increasing associated risks.

Methods: A Markov model simulated clinical and cost impacts to the patient and payers when a proportion of eligible patients with relapsing remitting multiple sclerosis (RRMS) discontinue DMT. Eligibility was defined as age >55 years, an RRMS diagnosis of >5 years, and no history of relapses for 5 years.

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Objectives: To examine the agreement between published reference resources for neurofilament light chain (NfL) applied to a large population of people with multiple sclerosis (MS).

Methods: Six published reference resources were used to classify NfL in participants in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network as elevated or normal and to derive age-specific NfL -scores. NfL values were classified as elevated if they exceeded the >95th percentile (i.

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Background And Objectives: Ganglion cell + inner plexiform layer (GCIPL) thinning, measured by optical coherence tomography (OCT), reflects global neurodegeneration in multiple sclerosis (MS). Atrophy of the inner (INL) and outer nuclear layer (ONL) may also be prominent in progressive MS (PMS). The phase 2, SPRINT-MS trial found reduced brain atrophy with ibudilast therapy in PMS.

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Objective: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

Methods: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

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Background: Processing speed decline is a common manifestation of multiple sclerosis (MS). The processing speed test (PST) is a validated electronic cognitive assessment based on the Symbol-Digit Modalities Test, which is routinely administered as part of the multi-institutional Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) initiative. The longitudinal relationship between education, processing speed, and employment is unclear.

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Thalamic volume is associated with clinical disability in multiple sclerosis (MS) and is vulnerable to secondary neurodegeneration due to its extensive connectivity throughout the central nervous system (CNS). Using a model of autoimmune demyelination that exhibits CNS-infiltrating immune cells in both spinal cord white matter and optic nerve, we sought to evaluate neurodegenerative changes due to lesions affecting the spino- and retino-thalamic pathways. We found comparable axonal loss in spinal cord white matter and optic nerve during the acute phase of disease consistent with synaptic loss, but not neuronal cell body loss in the thalamic nuclei that receive input from these discrete pathways.

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The C-type lectin receptor Mincle is known for its important role in innate immune cells in recognizing pathogen and damage associated molecular patterns. Here we report a T cell-intrinsic role for Mincle in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Genomic deletion of Mincle in T cells impairs TH17, but not TH1 cell-mediated EAE, in alignment with significantly higher expression of Mincle in TH17 cells than in TH1 cells.

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Background: Socioeconomic disadvantage may be an important contributor to clinical outcomes in MS but is not well understood. Our objective was to examine the associations between Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage, with clinical outcomes.

Methods: We assessed the longitudinal association between MS Performance Test (MSPT) and quality of life in Neurological Disorders (Neuro-QoL) measures with ADI quartiles (Q1: lowest deprivation - Q4 highest deprivation) in relapsing remitting MS (RRMS) and progressive MS cohorts.

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Background: Therapeutic inertia (TI) is a worldwide phenomenon that affects 60 to 90% of neurologists and up to 25% of daily treatment decisions during management of multiple sclerosis (MS) patients. A large volume of MS patients are women of childbearing age, and desire for pregnancy is a complex variable often affecting MS care. The objective of this study was to determine the effect of desire for pregnancy on decisions to escalate treatment during management of MS patients.

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Patients with multiple sclerosis acquire disability either through relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins and the extent to which multiple sclerosis therapies delay disability accumulation. Using the Novartis-Oxford multiple sclerosis (NO.

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Background: The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain.

Methods: Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response.

Results: Three hundred twenty-two people with MS were included; 91.

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Background: Several studies have demonstrated reduced serological response to vaccines in patients treated with anti-CD20 agents. However, limited data exist surrounding the clinical effect of disease modifying therapy (DMT) use on vaccine efficacy.

Objectives: To investigate breakthrough coronavirus disease 2019 (COVID-19) in vaccinated people with multiple sclerosis (PwMS) on DMT.

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Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT).

Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs.

Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled.

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The coronavirus disease 2019 (COVID-19) pandemic has catalyzed the rapid adoption of telemedicine which encompasses synchronous and asynchronous interactions between patients and providers. In order to facilitate this rapid deployment, there has been numerous regulatory changes to ensure caregivers can effectively communicate with patients during this time. We illustrate a model where people, processes, and technology work together to address the comprehensive needs of multiple sclerosis (MS) patients.

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Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare fatal autosomal dominant vasculopathy associated with mutations in the TREX1 gene. Only one de novo case has been reported in the literature. We report the long-term clinical, radiological, and pathological presentation of a patient with a de novo and novel mutation in this gene.

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Background: Vitamin D deficiency is associated with increased disease activity in multiple sclerosis (MS), but its role in progressive MS has not been elucidated. The objective was to determine the correlation between vitamin D levels and visual parameters in primary progressive MS (PPMS) and secondary progressive MS (SPMS).

Methods: Serum 25-hydroxyvitamin D (25[OH]D) and 25-hydroxyvitamin D (25[OH]D) levels were obtained from the Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in MS (SPRINT-MS).

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