Characterisation of MS phenotypes across the age span using a novel data set integrating 34 clinical trials (NO.MS cohort): age is a key contributor to presentation

Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective: The objective of this study is to describe the Novartis–Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes. Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients’ baseline age, using phase III study data (≈8000 patients). Results: NO.MS contains data of ≈35,000 patients (>200,000 brain images from ≈10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%–75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment. Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity

Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions

Multiple sclerosis; SARS-COV-2 vaccination; Humoral immune responseEsclerosis múltiple; Vacunación SARS-COV-2; Respuesta inmune humoralEsclerosi múltiple; Vacunació SARS-COV-2; Resposta immune humoralBackground: 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; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. Conclusion: Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Biogen (Cambridge, MA, USA). Funding for writing and editorial support was provided by Biogen

Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype

OBJECTIVE: Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis. BACKGROUND: Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown. DESIGN/METHODS: SPRINT-MS was a randomized, placebo-controlled 96-week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three-way interaction linear-mixed model. Adjustment for differences in baseline demographics, disease measures, and brain size was explored. RESULTS: Analysis showed that there was a three-way interaction between the time, treatment effect, and disease phenotype (P \u3c 0.06). After further inspection, the overall treatment effect was primarily driven by patients with PPMS (P \u3c 0.01), and not by patients with SPMS (P = 0.97). This difference may have been due to faster brain atrophy progression seen in the PPMS placebo group compared to SPMS placebo (P \u3c 0.02). Although backward selection (P \u3c 0.05) retained age, T2 lesion volume, RNFL, and longitudinal diffusivity as significant baseline covariates in the linear-mixed model, the adjusted overall treatment effect was still driven by PPMS (P \u3c 0.01). INTERPRETATION: The previously reported overall treatment effect of ibudilast on worsening of brain atrophy in progressive MS appears to be driven by patients with PPMS that may be, in part, because of the faster atrophy progression rates seen in the placebo-treated group

Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions

The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs

Multiple sclerosis management during the COVID-19 pandemic

Altres ajuts: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The development of standardized data collection as part of routine clinical care through Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) was developed and implemented at CC, JH, and CEMCAT in partnership with Biogen. Biogen did not have involvement in study design, data analysis or interpretation, or manuscript preparation.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. To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery. 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. There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services. Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption

Multiple Sclerosis Patients With Depression Are More Likely To Subjectively Rate Their Vision Poorly (.pdf)

Depression is a common condition in patients with multiple sclerosis (MS), and is routinely assessed in our MS center using the Patient Health Questionnaire-9 (PHQ-9). Patient-reported outcomes (PRO) are increasingly utilized in clinics and in clinical trials to assess the impact of neurological symptoms on patients' function. The aim of this study was to determine if depression negatively affects a patient's rating of their visual function

Optical Coherence Tomography Macular Volume Correlates With Walking Speed in Patients with Multiple Sclerosis (.pdf)

Optical coherence tomography (OCT) is used to measure the thickness of the layers of the retina. In multiple sclerosis (MS), it is used to quantify the effects of optic neuritis or MS, monitor disease progression, and assess for complications of disease modifying therapy. OCT is being evaluated as a potential biomarker in MS, for use in clinics and in therapeutic trials. The aim of this study was to evaluate the relationship between retinal thickness with walking speed in patients with MS/clinically isolated syndrome (CIS)