Cost, efficacy and safety comparison between early intensive and escalating strategies for multiple sclerosis: a Systematic Review and Meta-analysis
Leonardo Pipek1, João Vitor Mahler1, Rafaela Farias Vidigal Nascimento2, Samira Luísa Apóstolos-Pereira1, Guilherme Diogo Silva1, Dagoberto Callegaro1
1Neurology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, 2Neurology, Centro Universitário FMABC, Santo André, São Paulo, Brazil
Objective:

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

Background:
ESC strategy consists in starting low-to-moderate-efficacy disease modifying drugs (DMDs) in the treatment of multiple sclerosis, upscaling to high-efficacy DMDs when facing evidence of active disease. EIT strategy, on the other hand, is based on starting high-efficacy DMDs as first-line therapy. The optimal strategy is unclear in patients with multiple sclerosis.
Design/Methods:

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).

Results:

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.

Conclusions:
EIT presents a higher efficacy in preventing disability progression, without harnessing safety or cost in a 5-years time horizon.
10.1212/WNL.0000000000201829