FutureMS Cohort Profile: A Scottish Multi-Centre Inception Cohort Study of Relapsing-Remitting Multiple Sclerosis

Abstract

Multiple Sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries the most common cause of progressive neurological disability in working age persons. However, there is significant between-subject heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate, or aggressive disease course is very limited. There is therefore a need for integrated predictive tools to inform individualised treatment decision making. FutureMS is a nationally-representative, prospective observation cohort study comprising 440 participants with a new diagnosis of relapsing remitting MS living in Scotland between May 2016 and March 2019. Established with the aim of addressing this need for individualised predictive tools, the cohort is designed to combine detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow up at year one is complete and longer-term follow up is planned, beginning at five years after first visit. The study aims to address the biology and determinants of disease heterogeneity in MS. Here we describe the cohort design and present a profile of the participants at baseline and one year of follow up.

Data-driven analysis shows robust links between fatigue and depression in early multiple sclerosis

“…Geographical and demographic characteristics of the cohort were comparable with those of patients with recently-diagnosed multiple sclerosis in Scotland as a whole, as confirmed by mandatory incidence register for multiple sclerosis in Scotland. 19,45 Median FSS was 35 (IQR 24 -47, range 9 -63), consistent with mild/moderate fatigue severity, and 218 participants (49.5%) reported significant fatigue (FSS ≥ 36). 23 Fatigue was more severe in females (Female Median 36, IQR 26 -48; Male Median 30, IQR 19.5 -44; Wilcoxon rank sum test with continuity correction p=0.01), but not significantly correlated with age at study entry (Spearman's Rho = 0.047, p=0.32).…”

“…The study participants were drawn from FutureMS, 19 a nationally representative cohort of patients with newly diagnosed relapsing remitting MS (RRMS) in Scotland. This cohort was estimated to capture 45% of persons diagnosed with RRMS in Scotland during the study period 19 with data collected at baseline and 12 months follow up. Detailed phenotyping of all participants included a wide range of clinical measures and structural brain MRI data.…”

“…Brain tissue volumes and whole brain T2 hyperintense lesion volume (WMH) were derived using longitudinal processing 20 implemented in FreeSurfer6.0 (http://surfer.nmr.mgh.harvard.edu/) and an in-house adjusted FLAIR thresholding method, 21 respectively. Full details of the cohort 19 and the MRI brain acquisition and analysis 22 have been described elsewhere. Informed consent was obtained prior to study entry according to the Declaration of Helsinki and ethical approval was granted by the South East Scotland Research Ethics Committee 02 (Reference: 15/SS/0233).…”

“…34 T25FW, 9-HPT and PASAT were transformed into Z-scores to increase comparability. 19 To aid interpretation we classified these variables into five domains as follows: "physical" (EDSS, 9-HPT, T25FW and BMI), "cognitive" (SDMT and PASAT), "affective" (GAD-7 and PHQ-9), "sleep" (SLEEP), "imaging" (WMH, cGM, BG and THALA), and fatigue (FSS). This classification was employed solely to aid interpretation of results and was not included during network estimation.…”

“…First, the data analysed in our study were drawn from the FutureMS cohort study, which showed geographically and demographically representative coverage of Scottish patients diagnosed with RRMS. 19 Secondly, none of the study participants had received DMDs at study baseline, which allowed us to examine the associations of interest without effects from DMDs at study baseline, and to contrast findings with those one year later, when 72.7% had commenced disease modifying therapy. Thirdly, in light of the deep phenotyping in the FutureMS cohort, we were able to employ a wide range of relevant clinical, neuropsychological and imaging phenotyping which allows a unique opportunity to examine the associations of fatigue with a broad range of relevant variables.…”