ABSTRACT
Many patients with relapsing-remitting multiple sclerosis (RRMS) initiate disease modifying therapy (DMT) soon after diagnosis with a lower or moderate efficacy therapy because of favourable prognostic factors, safety concerns, a preferred route of administration, or associated cost. This approach requires the treating neurologist to make an early assessment of therapeutic response in the first 1-2 years on DMT and plan strategically for the possible need to escalate therapy. Clinicians should consider any breakthrough relapse, MRI changes, disability progression, and medication tolerability and adherence. Other outcome measures or biomarkers also may be incorporated into this assessment. The treating neurologist should be mindful of DMT mechanism of action and immunologic effects such as lymphopenia in relation to sequencing of medications. Advance attention to vaccination status, especially in the era of the COVID-19 pandemic, is important to avoid delays in escalating therapy. Recent evidence recommends against prolonged washout periods which have been associated with higher risk of new disease activity, particularly with escalation from fingolimod. While early aggressive therapy may become a common treatment paradigm, heterogeneity in MS disease severity, medication safety profiles, and patients' risk preferences suggest that the escalation approach will continue to be a viable paradigm.