MultiSCRIPT-Cycle 1—a pragmatic trial embedded within the Swiss Multiple Sclerosis Cohort (SMSC) on neurofilament light chain monitoring to inform personalized treatment decisions in multiple sclerosis: a study protocol for a randomized clinical trial
Authors: Janiaud Perrine , Zecca Chiara , Salmen Anke , Benkert Pascal , Schädelin Sabine , Orleth Annette , Demuth Lilian , Maceski Aleksandra Maleska , Granziera Cristina , Oechtering Johanna , Leppert David , Derfuss Tobias , Achtnichts Lutz , Findling Oliver , Roth Patrick , Lalive Patrice , Uginet Marjolaine , Müller Stefanie , Pot Caroline , Hoepner Robert , Disanto Giulio , Gobbi Claudio , Rooshenas Leila , Schwenkglenks Matthias , Lambiris Mark J. , Kappos Ludwig , Kuhle Jens , Yaldizli Özgür , Hemkens Lars G. 
Published: September 2024

Abstract
Background
Treatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS. sNfL might therefore be instrumental for a patient-tailored treatment adaptation. We aim to assess whether 6-monthly sNfL monitoring in addition to usual care improves patient-relevant outcomes compared to usual care alone.

Methods
Pragmatic multicenter, 1:1 randomized, platform trial embedded in the Swiss Multiple Sclerosis Cohort (SMSC). All patients with RRMS in the SMSC for ≥ 1 year are eligible. We plan to include 915 patients with RRMS, randomly allocated to two groups with different care strategies, one of them new (group A) and one of them usual care (group B). In group A, 6-monthly monitoring of sNfL will together with information on relapses, disability, and magnetic resonance imaging (MRI) inform personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified algorithms. In group B, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: (1) evidence of disease activity (EDA3: occurrence of relapses, disability worsening, or MRI activity) and (2) quality of life (MQoL-54) using 24-month follow-up. The new treatment strategy with sNfL will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Data collection will be embedded within the SMSC using established trial-level quality procedures.

Discussion
MultiSCRIPT aims to be a platform where research and care are optimally combined to generate evidence to inform personalized decision-making in usual care. This approach aims to foster better personalized treatment and care strategies, at low cost and with rapid translation to clinical practice.

Trial registration
ClinicalTrials.gov NCT06095271. Registered on October 23, 2023