OBJECTIVES: Multiple sclerosis (MS) is a neurodegenerative disease associated with long-term disability and significant economic impact. With the addition of new agents for the treatment of MS (e.g. natalizumab), there is a need to evaluate the relative value of newer therapies in terms of cost, given healthcare resource constraints in Brazil. This analysis considered just the indication for rapidly evolving severe relapsing-remitting multiple sclerosis (RESRRMS) patients (≥2 disabling relapses per year, and ≥1 gadolinium-enhancing lesions on brain magnetic resonance imaging or a significant increase in T2 lesion load). Brazilian reimbursement guidelines recommend natalizumab only as 3rd line treatment for MS. A budget impact analysis (BIA) has been created to analyze the impact of introducing natalizumab in RESRRMS treatment in Brazilian Public Healthcare System (SUS). METHODS: BIA was based on a Markov model with monthly cycles and 5-year time horizon with MS epidemiological data obtained from Brazilian public database (DATASUS). The model compared current MS treatment options reimbursed by the Brazilian government – interferons-betas, glatiramer acetate and natalizumab (3rd line) with an alternative scenario with 1st line natalizumab. RESULTS: The number of Brazilian patients eligible for REHARRMS treatment was estimated to be 1,574, 532 and 110 patients for 1st, 2nd and 3rd line treatment, respectively, in the first year. Compared to the current scenario, the inclusion of natalizumab in the reimbursement protocol for 1st line shows potential savings of USD 729.1K, 524.6K, 360.3K, 200.6K and 83.6K for 5 consecutive years.  CONCLUSIONS: The inclusion of natalizumab as RESRRMS treatment option is estimated to yield savings of USD 1.9 M in five years for MS treatment in SUS.