Disease-Modifying Therapies in Multiple Sclerosis: High-Efficacy Versus Escalation Approach

Abstract

Introduction: Early high-efficacy disease-modifying therapy (DMT) (e.g., alemtuzumab, ocrelizumab, natalizumab) may prevent long-term disability better than the traditional escalation strategy (first-line interferon/glatiramer, then stepping up). Methods: Systematic review of 8 RCTs and 12 observational studies (n=11,234) comparing high-efficacy DMT as initial treatment versus escalation from low-efficacy DMT. Primary outcome: time to confirmed disability progression (CDP, EDSS increase ≥1.0 sustained 6 months). Secondary: annualized relapse rate (ARR), brain atrophy rate. Results: High-efficacy first-line reduced CDP risk by 38% (HR 0.62, 95% CI 0.48–0.80) and ARR by 57% (RR 0.43) over 5 years. Brain atrophy rate was slower (–0.28% vs –0.43% per year). However, serious adverse events (PML, infusion reactions) occurred in 4.2% of high-efficacy group versus 0.7% in escalation group. Discussion: The benefit-risk trade-off favors high-efficacy in aggressive or highly active MS. In mild MS, escalation remains appropriate. Conclusion: High-efficacy DMT as initial therapy reduces disability progression in active multiple sclerosis but requires careful safety monitoring.