Strategies for Adaptive Follow-up and Evaluation - Guiding Use of Indicators for De-Escalation in Multiple Sclerosis

Due to the increasing scientific efforts in recent years, a variety of HET are now available for patients with MS. In addition to long-term clinical assessment, monitoring by means of magnetic resonance imaging (MRI) has also become increasingly established. No evidence of disease activity under appropriate immunotherapy has thus been defined in a wide variety of concepts using clinical and MRI parameters. These medical achievements have positively influenced the natural course of MS, especially by significantly reducing the relapse activity. In contrast, however, the risk of potential complications under long-term immunotherapy should not be underestimated. This concerns in particular infection risks but also an increased malignancy risk for various, mostly highly effective immunotherapies.

Therefore, the question increasingly arises in clinical practice as to what extent HET should be continued or should be de-escalated in case of long-term disease course. As patients and doctors take clinical decision to de-escalate their therapies, often after many years of little or even no disease activity, the central question of how to best monitor patients subsequently remains. Digital smartwatch-based measurements or app-based regular assessments could add high-frequency real-world data to the picture and thus improve the understanding of individual disease courses. Additionally, novel serological markers to detect neuronal damage are becoming more widely available. Consequently, this study aims to evaluate different digital measurements and blood-based analyses to monitor disease activity in MS patients, which have independently with their treating physicians decided to discontinue or de-escalate their disease-modifying treatment of MS.

Data captured by the used smartwatches (Withings Scanwatch) includes activity-related data (step count, minutes in certain intensity levels), basic cardiovascular measurements such as heart rate, and sleep-related data (total time asleep, sleep efficiency and quality etc.). Blood-based measurements include serum neurofilament-light-chain (sNfL), glial fibrillary acidic protein (GFAP) and proteomic data. The investigators will attempt to closely analyze MS patients after de-escalating or discontinuation of immunotherapy using digital and serological biomarkers in order to detect possible increased disease activity. In addition to clinical assessment, structural MRI examinations will be optionally conducted in patients from core center at baseline and in month 12 and 24. Measurement parameters from clinical MRI examinations (lesion load) are also taken into account from the other study centers. In addition to that, patients from core center will undergo an Optical coherence tomography (OCT) measurement. OCT is a non-invasive, interferometric method that allows for detailed visualization of retinal morphology and is known to reveal abnormalities in various central nervous system (CNS) disorders. Data will be collected for a 24-month prospective period.

• EDSS: Change From Baseline in Expanded Disability Status Scale (EDSS) Score [Time frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)]
• Change From Baseline in World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Score [Time frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)]
• Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component Paced Auditory Serial Addition Test [Time frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)]
• Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component 9-hole peg test [Time frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)]
• Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component Timed 25-foot walk (T25FW) [Time frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)]
• Change in Pittsburgh Sleep Quality Index (PSQI) [Time frame: Time frame: Screening + Baseline (V1), After 6 months (V2), After 12 months (V3), After 18 months (V4), After 24 months (V5)]
• Change From Baseline in Fatigue Severity Scale (FSS) [Time frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)]
• Change in Blood analysis (levels of sNfl, GFAP, serum proteomics) [Time frame: Time frame: Screening + Baseline (V1), After 6 months (V2), After 12 months (V3), After 18 months (V4), After 24 months (V5)]
• Questionnaire about smartwatch usage (System Usability Score) [Time frame: After 6 months and 24 months of use]
• Wearing time of smartwatch (daily) [Time frame: during the entire observation period]
• Longitudinal development of activity parameter: step count [Time frame: during the entire observation period]
• Longitudinal development of activity parameter: approximate distance traveled (meter) [Time frame: during the entire observation period]