Multiple sclerosis (MS) is among the most common causes of disability in the young and, despite the advent of highly effective disease-modifying therapies, remains an incurable disease. Prevention of MS before the onset of demyelination is a feasible, albeit ambitious, goal. Currently, preventive interventions with adequate evidence of efficacy are lacking, and evaluating such interventions with traditional trial designs is challenging. Additionally, the high frequency and low effect sizes of putative MS risk factors, a limited window of opportunity to intervene, and the relatively low incidence of MS in the general population make prevention studies conceptually and practically difficult. Nevertheless, studies in radiologically isolated syndrome have generated momentum within the MS prevention space, and novel trial designs offer the potential for reimagining traditional randomized controlled trials. In this Perspective, we discuss the challenges in developing and testing preventive interventions in MS and, drawing on progress in other diseases, we propose strategies and solutions. We discuss pragmatic approaches to risk stratification and illustrate the importance of considering statistical power and outcome definitions. Prevention studies require careful thought with respect to risk stratification, communication, intervention and outcomes but, given the current knowledge, the time to set up and start MS prediction and prevention studies is now.
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