This is a randomized pragmatic clinical trial fully embedded in the Swiss Multiple Sclerosis Cohort to assess whether sNfL biomarker monitoring improves patient-relevant outcomes and care of patients with relapsing-remitting (RR)MS by either increasing the proportion of patients with no evidence of disease activity (EDA) or by improving patients' health-related quality of life.

The course of multiple sclerosis (MS) is highly heterogenous with a large variability in symptoms, severity and response to treatment. A large majority of persons with MS are treated with disease modifying therapies (DMTs). DMTs can dramatically reduce even almost suppress relapses and occurrence of new lesions in magnetic resonance imaging (MRI) by weakening the immune system but which in turn may cause side effects such as opportunistic infections with prolonged treatment duration and intensity of the immunosuppression.

A more personalized approach to MS therapy is urgently needed to treat patients as little as possible but as much as necessary and at the right time. Such tailored strategies cannot be made without detailed information on treatment response and disease activity. Levels sNfL, which is released in the blood following neuroaxonal damage, has been shown to be associated with future MS disease activity, disability worsening, MRI activity and treatment response. sNfL might therefore be helpful for a patient-tailored treatment adaptation (e.g., escalation or de-escalation) ensuring disease stability, fewer adverse events and better quality of life. While sNfL is increasingly used as a marker of treatment response, its use in routine care is not yet widely established.

The SMSC is an observational study across 8 Swiss leading MS centers including >1600 participants with MS with a median follow-up of >5.7 years. The MultiSCRIPT project aims to use this real-world data infrastructure to systematically evaluate patient-relevant benefits resulting from innovations in MS patient care.

MultiSCRIPT goes beyond a unique trial but aims to be a sustainable learning system in which accumulating data from successive pragmatic randomized trials (i.e., learning cycles) enable the continuous generation of new hypotheses on how treatment and care strategies can be further personalized to treat patients as little as possible but as much as necessary at the right time. By being nested within the already existing and ongoing SMSC, this research infrastructure embedded in clinical care offers an unique opportunity to efficiently conduct a nationwide real-life evaluation of new care strategies, at low costs, and fostering evaluation and direct translation of effective innovations into usual care to improve patient outcome and quality of life. MultiSCRIPT-Cycle 1 is the first learning cycle.

Inclusion Criteria:

• Diagnosis of RRMS according to the most recent McDonald criteria (2017) for at least one year
• Have already consented to take part in the SMSC
• Age 18 years old or older
• Able and willing to consent

Exclusion Criteria:

• Inclusion or planned inclusion in another clinical trial that determines the drug therapy for MS for the purpose of research as these patients are most likely not following the SMSC usual care.