OBJECTIVES: Rheumatoid Arthritis (RA) leads to significant impact on management costs and patient’s quality of life. In Brazil, costs associated to RA patient’s care are 6.6-fold higher than general population, with greater resources consumption. Biologic treatment after two disease-modifying antirheumatic drugs fail is an alternative, but their high cost represents a challenge for decision makers. Currently, adalimumab, etanercept and infliximab are provided by the Brazilian public healthcare system. This study aims to assess the cost per responder of etanercept versus adalimumab and infliximab, for moderate to severe rheumatoid arthritis treatment from a public payer perspective in Brazil. METHODS: A decision-tree model was developed to simulate RA evolution after treatment with etanercept (basecase treatment), adalimumab or infliximab as first-line therapies and their associated costs over a 12-month time horizon. Therapy continuation or switch was evaluated at week 24. Effectiveness measure was ACR70 response. Direct medical costs included biologics, concomitant drugs, medical follow-up and adverse events management. Clinical response was extracted from published literature, while costs were collected from Brazilian public official databases. Probabilistic sensitivity analyses were performed through Monte Carlo Simulation second-order approach. RESULTS: In basecase analysis, 31.4%, 18.2% and 12.9% patients met ACR70 response for etanercept, adalimumab and infliximab. Annual costs per ACR70 responder were 147,147USD, 264,097USD and 327,632USD, respectively. Etanercept represented the least costly per ACR70 responder and the most effective alternative in all comparisons: 116,950USD and 180,485USD less than adalimumab and infliximab, respectively; 13.2% and 18.5% more patients met ACR70 response regarding adalimumab and infliximab. CONCLUSIONS: Etanercept exhibited incremental clinical effectiveness at a lower cost per ACR70 responders when compared to adalimumab and infliximab, from the Brazilian public health care system.