Consensus is lacking regarding the initiation and sequencing of disease-modifying therapies (DMTs) for management of multiple sclerosis (MS), resulting in variable use in clinical practice. As novel DMTs with different efficacy and safety profiles emerge based on clinical trials, it is increasingly important to compare the effectiveness and safety of DMTs in clinical practice. Comparing individual therapies in a pairwise fashion in a robust randomized clinical trial (RCT) is costly, rarely occurs, and may not generalize well to the clinical setting, given that clinical trial populations often exclude individuals with comorbidities and of extreme ages.1

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