OBJECTIVES: To use real-world data to evaluate the dynamics of the first treatment of multiple sclerosis (MS) with the available interferons (IFNs), within the Brazilian public healthcare system (SUS) and the average annual cost (AAC) of first and second treatments for current MS patients, and to simulate different scenarios for new patients within the next 12 months. METHODS: Data were extracted from the drug consumption database of Ambulatory Information System of the SUS (SIA-SUS) from January 2014 to February 2018. Patients initiating the available MS therapies within this period were included. Time between therapy switch and the weighted average for each IFN were calculated. AAC of treatment with first and second therapies were calculated for the patients currently being treated with IFNs as first treatment at the SUS, considering time between switch, chosen second treatment and annual costs of each therapy. For new patients, three different scenarios were simulated to estimate costs of therapy by varying the IFNs shares. RESULTS: Of the 11.740 naïve patients, 60% were using IFNs as their first treatment. AACs of treatment per patient were BRL18.950,80 for IFN β-1a intramuscular (IM) 30mcg, BRL19.026,65 for IFN β-1b subcutaneous (SC) 250 mcg and BRL21.950,21 for IFN β-1a SC 44 mcg. For the 1.693 estimated new patients, when the current IFN shares are applied (35,0% for IFN β-1a IM 30mcg, 15,7% for IFN β-1b SC 250 mcg and 49,3% for IFN β-1a SC 44 mcg), the estimated AAC of treatment is BRL34.604.986,37. Simulating 100% of new patients using IFN β-1a IM 30mcg, and 100% using IFN β-1a SC 44 mcg, estimated total AAC of treatment were BRL32.081.013,06 and BRL37.161.704,51 respectively. CONCLUSIONS: This study provides insights on how drugs within the same therapeutic area may differentially impact the costs of MS treatment, considering both acquisition costs and treatment duration.