OBJECTIVES: About 30% of patients treated with an anti-TNF agent failed to achieve an improvement of 20% in American College of Rheumatology (ACR) response. Recent clinical practice guidelines recommend the use of rituximab after previous failure of one anti-TNF. This study aims to assess the cost-effectiveness of rituximab compared to cycling between anti-TNF agents in this population from the perspective of the public health care system in Mexico. METHODS: A decision analysis was carried out to compare 2 rituximab courses (1 course, consisting of 2 infusions of 1g each) given 6 months apart; infliximab 3 mg/kg (weeks 0, 2, 6, 14) and 5 mg/kg (weeks 22, 30, 38 and 46); etanercept 25mg twice a week and adalimumab 40mg every other week. Only direct medical costs cumulated during a one-year timeframe were accounted for and these included acquisition cost of biologic drugs besides infusion costs for rituximab and infliximab. Primary efficacy outcome was defined as an improvement of 70% in ACR response (ACR70), which is a close measure of remission. Indirect comparison techniques were used to adjust ACR responses rates found in 9 clinical trials. Number needed to treat (NNT) to obtain an ACR70 was then calculated. All costs are reported in 2009 US dollars (USD). RESULTS: For a 70Kg patient, annual mean costs were estimated at USD$13,025 for rituximab, USD$12,938 for infliximab, USD$12,226 for adalimumab and USD$10,850 for etanercept. Adjusted ACR70 rates were higher in rituximab (12.4%) than in adalimumab (9.0%), etanercept (8.2%) and infliximab (5.4%). Average cost to achieve an ACR70 was lower with rituximab (USD$105,047) than with anti-TNF therapies, leading to savings of USD$27,270; USD$30,797 and USD$134,543 compared to etanercept, adalimumab and infliximab, respectively. CONCLUSIONS: This study suggests that rituximab treatment after previous failure of one anti-TNF agent is a cost-effective strategy compared to cycling between anti-TNF agents.