OBJECTIVES: Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with interferon beta (IFNβ) can develop neutralizing antibodies (NAbs) that reduce treatment efficacy. Several clinical studies explored the association of NAb+ status with increased disease activity. The impact of NAbs on costs has not been explored. The aim of this study was to estimate the cost of RRMS patients who develop NAbs while treated with IFNβ by the Italian National Healthcare Service (NHS) and the Italian Society perspectives. METHODS: The study was based on a mixed method approach, based on both already published observational clinical data from an Italian study in Bari of 546 RRMS patients treated with IFNβ, and cost data derived from the published literature. Direct and indirect costs were applied stratifying patients by EDSS 0-3 and 4-6.  The average rate of NAbs in IFNβ treated patients calculated in the Italian observational study was applied to the current Italian MS population treated with IFNβ. The values were inflated to Euro 2014. RESULTS: The direct cost per patient was estimated as €15,428 for the NAb+ and €14,317 for the NAb-. The annual societal cost per patient was estimated as €33,890 for the NAb+ and €30,790 for the NAb-. The  increase of the total annual costs specifically due to the NAb+ status was €3,100 from the Italian societal perspective and €1,111 from the Italian NHS perspective. Applying the average NAbs incidence rate, calculated in the Italian observational study (13.7%), to the current Italian MS population treated with IFNβ the total annual cost increases of approximately 3.5 million from the NHS perspective and 9.9 million from the societal perspective. CONCLUSIONS: The results of this economic evaluation suggest the association between Nab+ status and increased costs for the management of RRMS. Further pharmacoeconomic research will be needed to confirm this first result.