OBJECTIVES: Multiple sclerosis (MS) is a neurologic disease that can dramatically affect patients’ quality of life. The aim of this study is to conduct a cost-utility analysis of natalizumab (Tysabri®) versus interferon beta-1a 44 mcg (Rebif®) – a commonly prescribed 1st line disease modifying therapy – in rapidly evolving severe relapsing-remitting MS patients from the Brazilian Public Healthcare System (SUS) perspective. METHODS: A Markov model with 20-year time horizon with health states based on Expanded Disability Status Scale (EDSS) and disease relapses was developed. Since there are no published data evaluating long-term course specifically in RESRRMS, it was assumed transition probabilities on EDSS states were based on natural history studies in unselected RRMS patients, and relapse probabilities based on a post-hoc analysis of the placebo patients on pivotal natalizumab AFFIRM trial. In each monthly cycle, patients can discontinue treatment, remain stable, progress to higher EDSS state, experience progressive multifocal leukoencephalopathy (PML) or die. For natalizumab, we assumed efficacy data on disability progression and relapse from AFFIRM trial and for interferon beta-1a 44 mcg we assumed efficacy data on disability progression and relapse from pivotal trial PRISMS. Patients with EDSS score ≥ 7.5 receive best supportive care. Resource use and costs were validated by an expert panel and valued using Brazilian public official lists (DATASUS and BPS). Costs and outcomes were discounted (5%). Probabilistic sensitivity analyses covered variability in efficacy and costs. RESULTS: The use of natalizumab was associated with slower EDSS progression and reduced relapse burden. The quality-adjusted life years obtained with natalizumab and interferon beta-1a 44 mcg were 9.27 and 8.75, and costs were USD119,977 and USD132,446, respectively. In the base-case, natalizumab was dominant versus interferon beta-1a 44 mcg.  CONCLUSIONS: For a patient with HARRMS, the model shows that natalizumab was dominant when compared to interferon beta-1a 44 mcg in the Brazilian Public Healthcare System.