Highly effective disease-modifying treatment as initial MS therapy.

PURPOSE OF REVIEW: Using highly effective (HE) compounds right from the beginning of disease-modifying immunotherapy (DMT) in people with multiple sclerosis (pwMS) has gained popularity among clinicians and pwMS alike. We discuss the most recent evidence supporting this approach, and whether any of the associated risks should stop us adopting it as a default strategy. RECENT FINDINGS: With the addition of injectable ofatumumab, and the two oral sphingosine one phosphate modulators siponimod and ozanimod, ten HE DMTs are now available for pwMS, though variation in licensing status and cost may limit their use in some healthcare environments. Real World evidence based on large MS registry data suggests the superiority of early HE DMT over a slow treatment escalation approach; delaying HE DMT leads to more rapid and often irreversible disability accrual. Mechanistically, B-cell depletion, particularly memory B-cell suppression, is a common denominator closely associated with DMT efficacy. SUMMARY: The concept that HE DMTs are necessarily associated with a high risk of adverse effects, is no longer supported by the evidence. The rather predictable and manageable risk profile of most HE DMTs should lower the threshold for clinicians to discuss such treatment with pwMS as a first line approach.