Efficacy and Safety of High-Efficacy Versus Moderate-Efficacy DMTS in Early Relapsing-Remitting Ms: A Narrative Review

Background: The therapeutic landscape for relapsing-remitting multiple sclerosis (RRMS) has expanded dramatically, offering a spectrum of disease-modifying therapies (DMTs) with varying efficacy and safety profiles. A central debate in contemporary MS care is the choice between an early intensive strategy using high-efficacy DMTs and an escalation approach starting with moderate-efficacy agents. Objective: This narrative review critically evaluates the current evidence comparing the efficacy and safety of high-efficacy versus moderate-efficacy DMTs when initiated early in the course of RRMS, with reference to clinical trials, real-world observational studies, and international treatment guidelines from 2020 onward. Methods: A comprehensive literature search was conducted across PubMed, Embase, and the Cochrane Library for studies published between January 2015 and February 2026, using keywords including “relapsing-remitting multiple sclerosis,” “disease-modifying therapy,” “high-efficacy,” “moderate-efficacy,” “early intensive,” and “escalation.” Randomized controlled trials, observational cohort studies, meta-analyses, and systematic reviews were eligible. Key Findings: High-efficacy DMTs consistently demonstrate superior control of relapses and MRI lesion activity compared to moderate-efficacy agents. Landmark studies indicate that early initiation of high-efficacy therapy is associated with a significantly reduced risk of long-term disability accumulation, including progression independent of relapse activity (PIRA), with one study reporting a hazard ratio of 7.05 for PIRA with low-/moderate-efficacy DMTs versus high-efficacy therapies. However, this benefit is most pronounced in younger patients and may diminish with age. The risk of serious adverse events, including opportunistic infections, is higher with high-efficacy agents, necessitating rigorous risk stratification. A significant effect on reducing brain atrophy may require sustained treatment over 24 months for both categories. Conclusion: An early high-efficacy treatment approach offers superior disease control in young patients with highly active RRMS, aligning with a growing consensus toward proactive management. However, the benefits must be carefully weighed against higher short-term risks. An escalation strategy remains a viable option for patients with less active disease or higher baseline risk profiles, where long-term outcomes may be comparably favorable with a better initial safety margin.