Digital signatures of fatigue and wearing-off symptoms in patients with multiple sclerosis under natalizumab
9 affiliations
- 1Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, Düsseldorf, 40225, Germany; Hasso Plattner Institute, University of Potsdam, Potsdam, Germany
- 2Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, Düsseldorf, 40225, Germany
- 3Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, Düsseldorf, 40225, Germany
- 4Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland
- 5Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany
- 6Department of Neurology, University Hospital Muenster, Muenster, Germany
- 7Department of Neurology, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Germany
- 8Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, Düsseldorf, 40225, Germany; Department of Neurology, University Hospital Muenster, Muenster, Germany
- 9Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, Düsseldorf, 40225, Germany; Corresponding author.
Abstract
Wearing-off symptoms (WoS) during natalizumab (NTZ) treatment are frequently interpreted as subclinical disease activity in patients with multiple sclerosis (PwMS), but their significance remains uncertain. In the prospective single-center SATURATE study (NCT05701423), we investigated whether WoS were associated with inflammatory or neurodegenerative damage and whether wearable monitoring captures related motor changes. Thirty-four NTZ-treated participants were enrolled; 28 completed 6-month follow-up and 21 provided analyzable smartwatch data. Clinical assessments were performed at baseline, month 3, and month 6; serum NTZ, soluble vascular cell adhesion molecule-1, neurofilament light chain, glial fibrillary acidic protein, and diffusion-weighted magnetic resonance imaging were assessed at baseline and month 6. Before each NTZ administration, participants completed a WoS questionnaire. WoS occurred in 19/28 analyzed participants (67.9%) and 63/177 of observed questionnaires (35.6%). WoS rate was associated with fatigue, but not with dosing interval, diffusion changes, or serum biomarkers. The adjusted subcutaneous-versus-intravenous coefficient was −0.296 (HC3-robust 95% CI, −0.649 to 0.056; p = 0.100; conventional OLS 95% CI, −0.575 to −0.018; p = 0.038). Wearable data showed a subtle end-of-cycle decline in afternoon steps (within-subject z-score difference, −0.130; 95% CI, −0.229 to −0.004; Holm-adjusted p = 0.015). Dynamic activity features, including morning-to-afternoon step ratios and reduced peak step variability, correlated with fatigue scores and WoS rate. These exploratory findings indicate that, in this clinically stable cohort, WoS under NTZ do not reflect ongoing inflammatory or neurodegenerative disease activity, but rather align with fatigue-related motor changes detectable by high-adherence passive wearables. Dynamic wearable activity metrics warrant evaluation as digital endpoints for fatigue-focused interventions and clinical care.
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BibTeX
@article{masanneck2026digital,
title = {{Digital signatures of fatigue and wearing-off symptoms in patients with multiple sclerosis under natalizumab}},
author = {Lars Masanneck and Elaine Trautmann and Judith von Pavel and Ramona Hagler and Marius Vach and Patricia Kirschner and Jan Voth and Melanie Schuette and Pascal Benkert and Jens Kuhle and Jörn Kaufmann and Marie Deffner and Nicholas Schwab and Steffen Pfeuffer and Sven G. Meuth and Marc Pawlitzki},
journal = {Neurotherapeutics},
year = {2026},
month = oct,
doi = {10.1016/j.neurot.2026.e01075},
url = {https://doi.org/10.1016/j.neurot.2026.e01075},
note = {CC BY},
}
RIS
TY - JOUR
TI - Digital signatures of fatigue and wearing-off symptoms in patients with multiple sclerosis under natalizumab
AU - Lars Masanneck
AU - Elaine Trautmann
AU - Judith von Pavel
AU - Ramona Hagler
AU - Marius Vach
AU - Patricia Kirschner
AU - Jan Voth
AU - Melanie Schuette
AU - Pascal Benkert
AU - Jens Kuhle
AU - Jörn Kaufmann
AU - Marie Deffner
AU - Nicholas Schwab
AU - Steffen Pfeuffer
AU - Sven G. Meuth
AU - Marc Pawlitzki
PY - 2026
DA - 2026/10/24
JO - Neurotherapeutics
DO - 10.1016/j.neurot.2026.e01075
UR - https://doi.org/10.1016/j.neurot.2026.e01075
AB - Wearing-off symptoms (WoS) during natalizumab (NTZ) treatment are frequently interpreted as subclinical disease activity in patients with multiple sclerosis (PwMS), but their significance remains uncertain. In the prospective single-center SATURATE study (NCT05701423), we investigated whether WoS were associated with inflammatory or neurodegenerative damage and whether wearable monitoring captures related motor changes. Thirty-four NTZ-treated participants were enrolled; 28 completed 6-month follow-up and 21 provided analyzable smartwatch data. Clinical assessments were performed at baseline, month 3, and month 6; serum NTZ, soluble vascular cell adhesion molecule-1, neurofilament light chain, glial fibrillary acidic protein, and diffusion-weighted magnetic resonance imaging were assessed at baseline and month 6. Before each NTZ administration, participants completed a WoS questionnaire. WoS occurred in 19/28 analyzed participants (67.9%) and 63/177 of observed questionnaires (35.6%). WoS rate was associated with fatigue, but not with dosing interval, diffusion changes, or serum biomarkers. The adjusted subcutaneous-versus-intravenous coefficient was −0.296 (HC3-robust 95% CI, −0.649 to 0.056; p = 0.100; conventional OLS 95% CI, −0.575 to −0.018; p = 0.038). Wearable data showed a subtle end-of-cycle decline in afternoon steps (within-subject z-score difference, −0.130; 95% CI, −0.229 to −0.004; Holm-adjusted p = 0.015). Dynamic activity features, including morning-to-afternoon step ratios and reduced peak step variability, correlated with fatigue scores and WoS rate. These exploratory findings indicate that, in this clinically stable cohort, WoS under NTZ do not reflect ongoing inflammatory or neurodegenerative disease activity, but rather align with fatigue-related motor changes detectable by high-adherence passive wearables. Dynamic wearable activity metrics warrant evaluation as digital endpoints for fatigue-focused interventions and clinical care.
SN - 1878-7479
SN - 1933-7213
ER -