FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis

Abstract

Purpose: Multiple sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries is the most common cause of progressive neurological disability in working age persons. While treatable, there is substantial interindividual 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.

Participants: Established with the aim of addressing this need for individualised predictive tools, FutureMS is a nationally representative, prospective observational cohort study of 440 adults with a new diagnosis of relapsing-remitting MS living in Scotland at the time of diagnosis between May 2016 and March 2019.

Findings to date: The study aims to explore the pathobiology and determinants of disease heterogeneity in MS and combines detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow-up at year 1 is complete. Here, we describe the cohort design and present a profile of the participants at baseline and 1 year of follow-up.

Future plans: A third follow-up wave for the cohort has recently begun at 5 years after first visit and a further wave of follow-up is funded for year 10. Longer-term follow-up is anticipated thereafter.

Keywords: epidemiology; internal medicine; multiple sclerosis; neurogenetics; neurology; neuroradiology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Map of FutureMS participants by approximate location of residence at the time of diagnosis. Participant locations are not precise, located at the population centroid of the nearest SIMD intermediate zone (mean population ~4000). FutureMS cases (purple) are displayed alongside intermediate zone of residence of a random selection of 440 individuals from the SMSR (green). All map positions have latitudinal and longitudinal random noise added to prevent personal identifiability. MS, multiple sclerosis; SIMD, Scottish Index of Multiple Deprivation; SMSR, Scottish Multiple Sclerosis Register.

Figure 2

FutureMS cohort design. 9HPT, Nine Hole Peg Test; BMI, body mass index; BP, blood pressure; CRP, C reactive protein; EDSS, Extended Disability Status Scale; FBC, full blood count; HbA1C, glycosylated haemoglobin A1C; LFT, liver function test panel; MS, multiple sclerosis; OCT, optical coherence tomography; PASAT, paced auditory serial addition test 3; PBMC, peripheral blood mononuclear cells; SDMT, symbol digit modality test; T25W, Timed 25foot walk test; U&E, urea and electrolytes and renal function tests.

Figure 3

Density plots stratifying the cohort at baseline visit. (A) Distribution of EDSS (a measure of physical disability) by smoking status. (B) Evidence of greater burden of depression as detected by PHQ9 in those who are unemployed at baseline. EDSS, Expanded Disability Severity Score.

Figure 4

Physical measures of disability across the cohort at baseline and month 12. 9-HPT is the mean between hands of the mean of two attempts at the 9-HPT with each hand and is a measure of upper limb disability measured in seconds (longer time reflects less dexterity). EDSS is an ordinal scale where higher scores reflect greater disability. MSFC is a continuous scale (z-score) where lower values reflect greater disability, participants who are unable to walk are arbitrarily attributed very low Z-scores for the walking component of their test (−13.7) as per published instructions. This gives a long negative tail to the distribution as the −13.7 is chosen to allow for the cohort to progress in disability with time and still capture variance in walking ability. 9HPT, Nine Hole Peg Test; EDSS, Expanded Disability Severity Score; MSFC, Multiple Sclerosis Functional Composite score.

Figure 5

Individual level change in physical disability between the waves. (A) Outlier participants who have worsened or improved over the course of wave one are compared in B&C for their Fatigue Severity Score (FSS) at baseline and age at diagnosis. Circle size reflects size of difference between MSFC measurements between study visits (squared residual from least squares regression line of MSFC at year 1 on MSFC at year two). Outlier groups defined as above the 90th and below the 10th centile for regression residual. MSFC, Multiple Sclerosis Functional Composite score.

Figure 6

Fatigue Severity Score (FSS), PHQ-9 screening tool for depression, Symbol Digit Modality Tool (SDMT), Paced Serial Addition Tool (PASAT-3). Higher scores on Fatigue Severity Scale indicate worse fatigue. Higher scores on PHQ-9 indicate risk of depression. Higher scores on PASAT and SDMT indicate better performance on cognition testing and less impairment.

Figure 7

Correlation between adjusted measures of MS disease severity (MSSS and ARMSS). Size and colour of the points reflects the patient determined diseases steps a patient reported outcome. In these figures, points are study individuals, and the size and colour of the points are scaled using the PDDS (range 0–7, where 7 is most severe). ARMSS, Age-related Multiple Sclerosis Severity Score; MS, multiple sclerosis; MSSS, Multiple Sclerosis Severity Score; PDDS, Patient Determined Disease Steps.

Figure 8

Clinical and radiological measures at baseline visit stratified by HLA-DRB1*15:01 genotype. FSS, Fatigue Severity Scale; EDSS, Expanded Disability Severity Score; PDDS, Patient Determined Disease Steps; SDMT, symbol digit modality test; WMH, white matter hyperintensity.