Anchor-based evaluation of digital motor biomarkers from a 2-year observation in 100 patients with multiple sclerosis

BACKGROUND: Description of disease progression in MS lack sensitive clinical outcomes. Digital motor outcomes (DMO) offer potential but require thorough validation. OBJECTIVE: This 2-year observational study explores the sensitivity of 26 DMO derived from a task-based assessment protocol via RGB-D camera. METHODS: One-hundred people with MS (pwMS) were enrolled, 96 completed follow-up. Expanded Disability Status Scale (EDSS) and 12-Item MS Walking Scale (MSWS-12) served as anchors for sensitivity by classifying progression, improvement or stable at 2 years, irrespective of intercurrent relapses. Primary analysis applied linear mixed modeling. Distribution-based thresholds (MDC) were calculated from stable subgroups. RESULTS: Six DMO showed a significant increase over time in relation to stand-up/sit-movement (β = 0.01; β = 0.02), stepping asymmetry (β = 0.02; β = 0.02), trunk deflection while walking (β = 0.02) and trunk sway in closed-eyes stance (β = 0.02) (95% CI 0.001-0.038; all p < 0.05). EDSS (n = 22) and MSWS-12 (n = 11) progression groups were distinct. Time effects differed by anchor. For the EDSS progression group, the change in step width and sway velocity in closed-feet/open-eyes stance exceeded measurement error. CONCLUSIONS: Our findings yield a well-applicable set of DMO that may support definitions of disability accumulation in (early) pwMS. Establishing patient relevance remains challenging due to expectedly low clinical progression rates. The distinct patterns captured by EDSS and MSWS-12 definitions underline the need for multiple anchors when validating new biomarkers.