Association of Continuous Assessment of Step Count by Remote Monitoring With Disability Progression Among Adults With Multiple Sclerosis

Abstract

Importance: Disability measures in multiple sclerosis (MS) fail to capture potentially important variability in walking behavior. More sensitive and ecologically valid outcome measures are needed to advance MS research.

Objectives: To assess continuous step count activity remotely among individuals with MS for 1 year and determine how average daily step count is associated with other measures of MS disability.

Design, setting, and participants: In a prospective longitudinal observational cohort study, 95 adults with relapsing or progressive MS who were able to walk more than 2 minutes with or without an assistive device were recruited between June 15, 2015, and August 8, 2016, and remotely monitored in their natural environment for 1 year. Patients were excluded if they had a clinical relapse within 30 days or comorbidity contributing to ambulatory impairment. Longitudinal analysis was performed from October 2017 to March 2018. Revised analysis was performed in December 2018.

Intervention: Activity monitoring of step count using a wrist-worn accelerometer.

Main outcomes and measures: Average daily step count compared with in-clinic assessments and patient-reported outcomes.

Results: Of the 95 participants recruited (59 women and 36 men; mean [SD] age, 49.6 [13.6] years [range, 22.0-74.0 years]), 35 (37%) had progressive MS, and the median baseline Expanded Disability Status Scale score was 4.0 (range, 0-6.5). At 1 year, 79 participants completed follow-up (83% retention). There was a modest reduction in accelerometer use during the 1 year of the study. A decreasing average daily step count during the study was associated with worsening of clinic-based outcomes (Timed 25-Foot Walk, β = -13.09; P < .001; Timed-Up-and-Go, β = -9.25; P < .001) and patient-reported outcomes (12-item Multiple Sclerosis Walking Scale, β = -17.96; P < .001). A decreasing average daily step count occurred even when the Expanded Disability Status Scale score remained stable, and 12 of 25 participants (48%) with a significant decrease in average daily step count during the study did not have a reduction on other standard clinic-based metrics. Participants with a baseline average daily step count below 4766 (cohort median) had higher odds of clinically meaningful disability (Expanded Disability Status Scale score) worsening at 1 year, adjusting for age, sex, and disease duration (odds ratio, 4.01; 95% CI, 1.17-13.78; P = .03).

Conclusions and relevance: Continuous remote activity monitoring of individuals with MS for 1 year appears to be feasible. In this study, a decreasing average daily step count during a 1-year period was associated with worsening of standard ambulatory measures but could also occur even when traditional disability measures remained stable. These results appear to support the prospect of using the average daily step count as a sensitive longitudinal outcome measure in MS and as a clinically relevant metric for targeted intervention.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bove reported receiving personal fees from Novartis, Roche-Genentech, and Genzyme-Sanofi; and receiving grants from Akili Interactive outside the submitted work. Dr Graves reported receiving personal fees from Novartis outside the submitted work. Dr Romeo reported receiving grants from the National Multiple Sclerosis Society outside the submitted work. Dr Green reported serving on scientific advisory boards or trial execution committees for MedImmune (VielaBio), Novartis, Inception 5 Sciences, Pipeline, and Bionure; holding a patent for remyelination molecules and pathways; receiving research support from Novartis, Inception Sciences, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the National Institutes of Health, National Multiple Sclerosis Society, Sherak Foundation, and Hilton Foundation; and serving as an expert witness in Mylan Pharmaceuticals v Teva Pharmaceuticals. Dr Olgin reported receiving grants from Zoll; and personal fees from Novartis and from Vivalink outside the submitted work. Dr Marcus reported receiving grants from Jawbone Health during the conduct of the study. Dr Cree reported receiving personal consulting fees from AbbVie, Akili, Biogen, EMD Serono, GeNeuro, and Novartis outside the submitted work. Dr Gelfand reported receiving grants to University of California, San Francisco from Genentech; receiving service contract support to University of California, San Francisco from MedDay; receiving personal fees from Alexion and from Biogen outside the submitted work; and receiving personal compensation for medical legal consulting and serving as an expert witness outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Accelerometer Use in a Prospective Research Cohort of Individuals With Multiple Sclerosis (MS) During a 1-Year Period

A, Accelerometer use during the 1-year study period. Each bar represents the number of participants with valid Fitbit data (≥128 average daily steps per day, ≥3 days per week) during the 1-year study. B, Individual participant-level data by month, depicting periods of use and disuse of the wrist-worn accelerometer for 12 months. Each dot represents valid accelerometer data collected for 1 individual participant for that month.

Figure 2.. Change in Average Daily Step Count Stratified by Expanded Disability Status Scale (EDSS) Score

A, Change in continuous average daily step count per week during a 1-year period, stratified by clinically meaningful change in EDSS score. B. Change in average daily step count per week during a 1-year period among individuals with a stable EDSS score (groups with EDSS scores of 4.0 and 4.5-5.5 were combined to achieve an adequate sample size). C, Change in average daily step count per week during the 1-year study by EDSS group. In each panel, the shaded area represents the 95% CIs for the regression line, and each point reflects the daily step count averaged per week (using weighted means) for individuals who had clinically meaningful worsening, improvement, or no change in EDSS score during a 1-year period (52 weeks).

Figure 3.. Number of Participants With Worsening in Expanded Disability Status Scale (EDSS) Score, Timed 25-Foot Walk (T25FW), or Average Daily Step Count During the 1-Year Study

The horizontal bar graph to the left shows the number of participants who worsened in each of the 3 outcomes. The vertical bar graph to the right shows the shared number of participants (intersection size) who worsened during the year for 1 or more of the 3 outcomes, depicting each combination separately. A blue circle indicates whether that group of participants exhibited 1 or more of the 3 listed outcomes in the corresponding matrix cell. An orange circle indicates that that group of participants did not exhibit that outcome. A vertical blue line illustrates the column-based associations by indicating overlap (eg, a group with 2 blue circles connected by a vertical blue line exhibited both of those listed outcomes).

Figure 4.. Average Daily Step Count per Week Compared With the Change in Clinic-Based and Patient-Reported Outcomes

Each point reflects the average daily step count averaged per week (using weighted means) of individuals with changes in clinic-based and patient-reported outcomes from baseline to 1-year follow-up. The shaded areas represent the 95% CIs for the regression line. MSWS-12 indicates 12-item Multiple Sclerosis Walking Scale; TUG, Timed-Up-and-Go; and T25FW, Timed 25-Foot Walk.