Evaluating approved and off-label treatment strategies for real world multiple sclerosis patients – a precision medicine approach

Multiple sclerosis (MS), a chronic inflammatory and neurodegenerative condition, is a major cause of disability and driver of healthcare costs among young and middle aged adults. Access to a range of disease-modifying treatments (DMTs) have improved outlooks for most patients.

Major knowledge gaps remain on the benefit-risk balance of specific DMTs strategies in real world populations, however, with little evidence to guide the choice of DMT for individual patients.

This prompted us to launch Combat-MS, a nationwide observational drug trial following 3500 participants from 2017 to 2022 to answer which initial or secondary DMT strategy that, at the group level, best preserves quality of life and neurological functions.

Nearing its end, the study has generated important insights on safety/effectiveness of major DMTs, also gaining major international interest.

With this proposal, we wish to expand the cohort with further national registry and biomarker data and implement new prediction techniques to move from the group level to more individualized prognostication, including how DMT switches or extended dosing intervals interact with patient characteristics to predict treatment outcomes, and with a special focus on off-label use of rituximab.

Analyzing this rich data with state-of-the art biostatistics and machine learning, we will build a framework for a precision medicine approach to MS, evaluating the benefit-risk of distinct DMT strategies across diverse MS populations.