OBJECTIVES: To evaluate the cost-effectiveness of etanercept combination therapy with methotrexate (MTX) versus rituximab with MTX for rheumatoid arthritis (RA) from a payer’s perspective in Colombia. METHODS: A literature-based decision analytic model was constructed with a one year time horizon to compare the cost-effectiveness of etanercept 25mg twice-weekly+MTX versus rituximab 2x1000mg infusion+MTX in RA patients with an inadequate response to disease-modifying anti-rheumatic drugs. The primary measure of clinical effectiveness was based on remission (Disease Activity Score 28 joint count<2.6). The model incorporated major and minor infectious events, discontinuation due to lack of efficacy or adverse event, and rituximab re-treatment within the one year time-horizon. Drug costs were based on average wholesale price. Cost of managing adverse events and infusion costs were compiled based on queries to Colombian rheumatologists. Sensitivity analysis was conducted in the ±30% price range and efficacy parameters for etanercept and rituximab. RESULTS: One year total treatment costs for rituximab were COL$37,442,828 and COL$39,825,456 for etanercept. The percent of patients achieving remission was 3% for rituximab and 27% for etanercept at the end of 1 year. The incremental cost-effectiveness ratio (ICER) was COL$9,931,754 per additional patient achieving remission. The number needed to treat was 29 for rituximab and 5 for etanercept. Given a hypothetical budget of COL$1,000,000,000, the number of patients achieving remission was 7 for etanercept and 1 for rituximab. Sensitivity analysis showed that etanercept continued to have more patients achieving remission than rituximab even if the drug cost and efficacy was varied by ±30% given a defined budget. CONCLUSIONS: The results suggest that etanercept appears to be cost-effective compared to rituximab. Additionally, more patients can be successfully treated to remission with etanercept than rituximab given a defined budget. These findings were robust for plausible ranges of effectiveness and drug acquisition costs.