Our goal was to compare the effectiveness, safety, and cost between Escalating (ESC) and Early intensive (EIT) strategies for the treatment of multiple sclerosis.

We searched MEDLINE, EMBASE, and SCOPUS until September 4th, 2022 for studies comparing EIT and ESC strategies in adult patients with relapsing-remitting multiple sclerosis and a minimum follow-up of 5 years. Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year time horizon were the main outcomes. Economic analysis followed a Markov model using previously described transition matrix, utility and costs of multiple sclerosis and DMDs. Bias assessment was performed using ROBINS-I. This review was registered with PROSPERO (CRD42022358097).

Seven studies involving 3,467 participants demonstrated a 30% reduction in the risk of EDSS worsening at 5 years (RR 0.7; [0.59-0.83]; p<0.001) in the EIT group. Safety profile was similar between EIT and ESC strategies (RR 1.92; [0.38-9.72]; p=0.4324). EIT group showed 0.03 increase in QALY and a reduction of £1506 in a 5-year time horizon model. EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and/or cladribine was cost-effective in our models.