Stride-level measurement of gait as an early sensitive marker of disability progression in ambulatory patients with multiple sclerosis

Background: Wearable digital health technologies offer a unique opportunity to assess gait at the stride level in real-world settings. Walking impairment is a major cause of disability in multiple sclerosis (MS), yet current clinical metrics lack sensitivity to early and progressive changes in mobility. Methods: We conducted two studies (NCT04888689/NCT04882891) using a wearable device to develop and validate digital mobility outcome measures based on individual strides in patients with MS. First, we assessed technical performance in a controlled, single-center environment between September 12 and September 18, 2021. We then conducted a 12-month longitudinal study under daily living conditions across six sites between March 2021 and January 2024. The evaluated metrics included stride velocity 95th centile, walking distance 90th centile, and strides per hour. Findings: The controlled and longitudinal studies included 21 and 78 participants, respectively. The device demonstrated high stride detection accuracy (precision: 0·99) and a mean absolute error in stride velocity of 0·019 m/s. In the longitudinal study, stride velocity 95th percentile showed excellent reliability (ICC (2,1) = 0·97, SEM = 0·06) and strong agreement with Expanded Disability Status Scale (Spearman's rho = 0·65, p < 0·001) and Timed 25-Foot Walk (Spearman's rho = -0·71, p < 0·001), sensitivity to 12-month progression in both relapsing-remitting and progressive MS (p = 0·049 and p = 0·006, respectively), outperforming the Expanded Disability Status Scale. Walking distance 90th percentile and strides per hour were reliable and valid but less sensitive to progression. Interpretation: Stride velocity 95th percentile derived from real-world, stride-level data, provides a valid, reliable, and sensitive digital outcome for detecting MS progression. It may serve as an early indicator of progression and support the accelerated evaluation of treatments targeting progression. Funding: This study was funded by F. Hoffmann-La Roche Ltd.