Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation. In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation

European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)-COST action 15111-from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS

Symptomatology of multiple sclerosis relapses varies in relation to demographic and clinical factors

Introduction: Our knowledge of incidence and outcomes of MS relapses with specific symptomatology is limited. For example, optic neuritis is more common in early MS and the ability to recover deteriorates with longer disease duration. However, a comprehensive evaluation of multiple sclerosis relapse phenotypes, comprising clinical presentations, severity, impact and recovery, and capturing full spectrum of MS courses, duration and patient demography, has not yet been done. Aim: To identify patterns of clinical MS relapses, their impact on specific neuroanatomical locations and their associations with demographic and clinical parameters. Methods: Information about relapse symptomatology was collected prospectively in 17,555 eligible patients and 104,333 patient-years recorded in MSBase, an international observational MS registry. In a proportion of the relapses, information about relapse severity, impact on activities of daily living and recovery was available. Associations between relapse phenotype and patient characteristics were tested with a series of multivariable logistic regression models. Principal component analysis was conducted to assess the tendency of the specific relapse locations to be involved sequentially in individual patients. Results: Of 63,343 relapses, the majority affected pyramidal and sensory functions. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were recorded mostly in earlier disease and less commonly in relapsing-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women more commonly presented with sensory or visual symptoms, while men were more prone to pyramidal, brainstem and cerebellar relapses. Relapses were likely to recur within the previously affected locations (odd ratios 1.8 – 5, p = 10^-13), with pyramidal, sphincter and sensory relapses often converging within the same individuals (eigenvalue = 2.1, loadings 0.59-0.68). Sensory relapses had a lower impact on daily activities and together with visual and brainstem relapses showed better recovery than the other relapse presentations. Finally, relapse severity increased and the ability to recover decreased with age or more advanced disease. Conclusions: Patterns of clinical relapse symptomatology vary with respect to demographic and clinical factors, including age, sex, MS duration, course and stage

Relapse incidence in women and men throughout the course of multiple sclerosis: An MSBase cohort study

Introduction: Only one large retrospective cohort study and several smaller analyses examined predictors of relapse incidence in MS. Sex, age and MS duration were suggested as determinants of relapse activity. While in relapsing-remitting MS women are overrepresented in the ratio of 3:1 to men, in primary progressive disease both sexes are represented equally. A lower probability of relapse in men could be the reason for this change, with primary progressive (PP) MS representing the “extreme” of low relapse activity. Aims: To evaluate effect of sex on the incidence of MS relapses. To assess the hypothesis that the female-to-male ratio increases gradually with relapse activity and that PPMS represents a non-relapsing extreme along this continuum. To directly compare effects of age and MS duration on relapse incidence. Methods: Annualised relapse rates were calculated using the MSBase registry. Patients with incomplete data or less than one year of follow-up were excluded. Patients with PPMS were only included in the sex ratio analysis. Relapse incidences over 40 years of MS duration or up to 70 years of age were compared between females and males using Andersen-Gill and Poisson models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and PPMS. All models were adjusted for therapy and pregnancy. Results: Among 11,570 eligible patients with relapse-onset MS (82,552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared to males. Within the initial five years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 to >=4 relapses per year, respectively. The magnitude of this sex effect increased at longer MS duration and older age. However, the female-to-male ratio in patients with relapse-onset MS and zero relapses in any given year was double that of the patients with PPMS. Patient age was a more important determinant of decline in relapse incidence than disease duration. Conclusions: Females are predisposed to higher relapse activity than males. However, this sex-related effect does not explain the markedly lower female-to-male ratio in PPMS. Decline in relapse activity over time is more closely related to patient age than MS duration. This information helps us better understand the effects of sex and time on relapse incidence and define PPMS as an entity distinct from the relapse-onset MS

Redefining the Multiple Sclerosis Severity Score (MSSS): the effect of sex and onset phenotype

L