Inflammatory disease in people with multiple sclerosis treated with immune checkpoint inhibitors.

This study evaluated disease activity in people with Multiple Sclerosis (PwMS) who received immune checkpoint inhibitors (ICIs) compared to PwMS not treated with ICIs. There were 108 PwMS included (27 PwMS+ICIs and 81 PwMS controls), matched on age, sex, disease duration, DMTs, and MS disease course. Of 27 PwMS+ICIs, one (4%) had a relapse and four (15%) developed new MRI lesions without clinical symptoms.

Differential Diagnosis of Suspected Multiple Sclerosis in Pediatric and Late-Onset Populations: A Review.

Importance: While the typical onset of multiple sclerosis (MS) occurs in early adulthood, 2% to 10% of cases initially present prior to age 18 years, and approximately 5% after age 50 years. Guidance on approaches to differential diagnosis in suspected MS specific to these 2 age groups is needed.

Observations: There are unique biological factors in children younger than 18 years and in adults older than age 50 years compared to typical adult-onset MS.

A 2-stage model of heterogenous treatment effects for brain atrophy in multiple sclerosis utilizing the MS PATHS research network.

Background: Two-stage models of heterogenous treatment effects (HTE) may advance personalized medicine in multiple sclerosis (MS). Brain atrophy is a relatively objective outcome measure that has strong relationships to MS prognosis and treatment effects and is enabled by standardized MRI.

Objectives: To predict brain atrophy outcomes for patients initiating disease-modifying therapies (DMT) with different efficacies, considering the patients' baseline brain atrophy risk measured via brain parenchymal fraction (BPF).

Efficacy of Ofatumumab and Teriflunomide in Patients With Relapsing MS From Racial/Ethnic Minority Groups: ASCLEPIOS I/II Subgroup Analyses.

Background And Objectives: Race and ethnicity may influence the efficacy of disease-modifying therapies in patients with multiple sclerosis (MS). Incidence of MS in ethnically diverse groups may be higher; however, these populations are under-represented in MS trials. This post hoc analysis compared the proportion of patients achieving 3-parameter no evidence of disease activity (NEDA-3) with ofatumumab vs teriflunomide in participants with relapsing MS (RMS) enrolled in the ASCLEPIOS I/II trials by race/ethnicity subgroup.

Comparing Cognitive Profiles in Older Adults With Multiple Sclerosis and Alzheimer Disease: More Similarities Than Differences.

Background And Objectives: Up to 65% of people with multiple sclerosis (MS) experience disease-related cognitive impairment, but even after decades of research, still very little is known about the cognitive issues among older adults with MS (EwMS; individuals aged 60+). To date, few studies have attempted to characterize cognitive impairment in this group or compare EwMS with those with other neurodegenerative diseases. Our goal was to address this knowledge gap by comparing EwMS with individuals experiencing cognitive impairment due to probable Alzheimer disease (AD) with biomarker confirmation.

Clinical and Treatment Considerations for the Pediatric and Aging Patients with Multiple Sclerosis.

Chronologic aging is associated with multiple pathologic and immunologic changes that impact the clinical course of multiple sclerosis (MS). Clinical phenotypes evolve across the lifespan, from a highly inflammatory course in the very young to a predominantly neurodegenerative phenotype in older patients. Thus, unique clinical considerations arise for the diagnosis and management of the two age extremes of pediatric and geriatric MS populations.

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.

Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: A real-world retrospective multicenter analysis.

Background: The prevalence of multiple sclerosis (MS) in older people is increasing due to population aging and availability of effective disease-modifying therapies (DMTs). Treating older people with MS is complicated by age-related and MS-related comorbidities, immunologic effects of prior DMTs, and immunosenescence. Teriflunomide is a once-daily oral immunomodulator that has demonstrated efficacy and acceptable safety in clinical trials of adults with relapsing forms of MS (RMS).

Dimethyl Fumarate Delays Multiple Sclerosis in Radiologically Isolated Syndrome.

Objective: The radiologically isolated syndrome (RIS) represents the earliest detectable pre-clinical phase of multiple sclerosis (MS). This study evaluated the impact of therapeutic intervention in preventing first symptom manifestation at this stage in the disease spectrum.

Methods: We conducted a multi-center, randomized, double-blinded, placebo-controlled study involving people with RIS.

Expert opinion on COVID-19 vaccines and cladribine tablets in MS: A plain language summary.

What Is This Summary About?: People with multiple sclerosis (shortened to MS) who are taking cladribine tablets may have concerns about whether they can be vaccinated against COVID-19. This summary details the findings from a previously published article, in which an international committee of 10 MS experts developed recommendations to answer some important questions about COVID-19 vaccines in people with MS (including relapsing-remitting or active secondary progressive disease) taking cladribine tablets.

What Were The Results?: The committee identified 13 recommendations, which were all agreed upon by at least three-quarters (75%) of the 38 voting MS experts.

Ageing and multiple sclerosis.

The factor that is most relevant and strongly associated with the clinical course of multiple sclerosis is chronological age. Very young patients exclusively have relapsing remitting disease, whereas those with later onset disease face a more rapid development of permanent disability. For people with progressive multiple sclerosis, the poor response to current disease modifying therapies might be related to ageing in the immune system and CNS.

Curriculum Innovations: Virtual Didactics as a Tool for Harmonizing Education About Rare Topics in Neuroimmunology.

Introduction And Problem Statement: Neuroimmunology is a rapidly evolving subspecialty. At this time, fellowship training is not standardized. Discrepancies exist in fellowship programs across the United States, including in faculty expertise in rarer neuroimmunologic conditions.

The Two Sides of Siponimod: Evidence for Brain and Immune Mechanisms in Multiple Sclerosis.

Siponimod is a selective sphingosine 1-phosphate receptor subtype 1 (S1P) and 5 (S1P) modulator approved in the United States and the European Union as an oral treatment for adults with relapsing forms of multiple sclerosis (RMS), including active secondary progressive multiple sclerosis (SPMS). Preclinical and clinical studies provide support for a dual mechanism of action of siponimod, targeting peripherally mediated inflammation and exerting direct central effects. As an S1P receptor modulator, siponimod reduces lymphocyte egress from lymph nodes, thus inhibiting their migration from the periphery to the central nervous system.

Consensus Curriculum for Fellowship Training in Multiple Sclerosis and Neuroimmunology.

Management of multiple sclerosis and neuroimmunologic disorders has become increasingly complex because of the expanding number of recognized neuroimmune disorders, increased number of therapeutic options, and multidisciplinary care management needs of people with multiple sclerosis and neuroimmunologic disorders. More subspecialists are needed to optimize care of these patients, and many fellowship programs have been created or expanded to increase the subspecialty workforce. Consequently, defining the scope and standardizing fellowship training is essential to ensure that trainees receive high-quality training.

Cognition and disease characteristics in adult onset versus late onset multiple sclerosis.

Background: Cognitive impairment is common sequelae of multiple sclerosis (MS); however, relatively little is known about cognitive impairment in late-onset multiple sclerosis (LOMS).

Objective: To investigate differences in disease characteristics and cognition in LOMS and adult-onset multiple sclerosis (AOMS) patients.

Methods: Archival medical records and neuropsychological evaluations from an MS specialty center were reviewed.

Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice.

Objective: To assess the real-world comparative effectiveness of switching from natalizumab (NTZ) to a moderate-efficacy (Mod) disease-modifying therapy (DMT) vs high-efficacy therapy (HET) in patients with multiple sclerosis (MS).

Methods: Patients discontinuing NTZ at two MS centers (n = 556) who switched to Mod DMT (n = 270) vs HET (n = 130) were assessed using propensity score (PS) weighting. PS model covariates included demographics and baseline clinical and MRI characteristics.

Clinical characteristics of a large multi-center cohort of people with multiple sclerosis over age 60.

Background: As the peak prevalence of multiple sclerosis (MS) shifts due to an aging patient population, understanding the characteristics that define this older cohort to improve overall management is critical. We sought to determine the clinical characteristics of people with MS over age 60.

Methods: Demographics, clinical characteristics, MS disease history, and Multiple Sclerosis Performance Test (MSPT) patient-reported outcomes and neuroperformance tests (NPTs) were collected from 10 academic MS centers in the US and Europe participating in the MS Partners Advancing Technology Health Solutions (MS PATHS) system.

Multiple sclerosis management during the COVID-19 pandemic.

Background: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services.

Objectives: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery.

Methods: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d'Hebron-Centre d'Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care.

Re-Evaluating the Use of IFN-β and Relapsing Multiple Sclerosis: Safety, Efficacy and Place in Therapy.

The advent of interferon therapy for the treatment of multiple sclerosis (MS) was a massive advancement in the field and changed the course of the disease. While the exact mechanism of interferon therapy in MS is unknown, disease control is likely mediated by reducing Th1 and Th17 cells while increasing regulatory T cells and altering the cytokine profile. Interferon therapy not only gave physicians and patients an evidence-based treatment option to treat MS by decreasing relapses and the accrual of disability but it also provided valuable insight into disease pathophysiology that allowed for the development of further treatments.

Outcomes and future directions for neuroimmunology/multiple sclerosis fellowship training: Survey of recent trainees.

Background: Neuroimmunology/multiple sclerosis is a rapidly evolving, but still poorly defined subspecialty. Fellowship training is not standardized, and there is substantial variability across sites. Outcomes of fellowship training have not yet been studied.

Education Research: Multiple sclerosis and neuroimmunology fellowship training status in the United States.

Objective: To investigate the current status of postgraduate training in neuroimmunology and multiple sclerosis (NI/MS) in the United States.

Methods: We developed a questionnaire to collect information on fellowship training focus, duration of training, number of fellows, funding application process, rotations, visa sponsorship, and an open-ended question about challenges facing training in NI/MS. We identified target programs and sent the questionnaires electronically to fellowship program directors.