OBJECTIVES: In the past years anti-TNF-a drugs have become a crucial component of the treatment of Rheumatoid Arthritis (RA). Recent health-policy decisions prove that in Germany initial choice of agents will increasingly depend on expected treatment costs and cost-effectiveness. In order to inform decision making we assessed the cost-effectiveness of Adalimumab (ADA), Etanercept (ETA), and Infliximab (INF) based on published real-world data from the German Biologics Registry. METHODS: We designed an excel-based model and calculated the costs per LUNDEX responder month. The LUNDEX score developed by Kristensen et al. (2006) is combining the proportion of patients fulfilling a response criterion (e.g. ACR 20) with therapy adherence. Our model compares the costs per LUNDEX-response over six months for the treatment with ADA, ETA and INF from a payer-perspective. ACR 20 response rates after six months (INF=46%, ADA=50%, ETA=58%), therapy adherence therapy (INF=77%, ADA=79%, ETA=82%) and real-world dosing data (INF=4mg/kg body weight, ADA=40mg/bw, ETA=47.5mg/week) were derived from published registry data. Drug, administration and lab costs were calculated using official databases. RESULTS: During the first six months, treatment with INF, ADA or ETA causes costs of 11,151 €, 8,542 € and EUR 9,936 €, respectively. The LUNDEX index at six months is 0.357 for INF, 0.395 for ADA and 0.477 for ETA. The costs per LUNDEX response are 21,626 € for ADA, 21,626 € for ETA and 31,210 € for INF. The average cost per LUNDEX-responder month in Germany is 3,901€ for ADA, 3,450 € for ETA and 5,162 € for INF during the first six months of treatment. CONCLUSION: Our analysis supports decision making based on a combined measure of response and therapy adherence. According to German registry data ETA seems to be the most cost-effective agent. Long-term data on response and adherence are needed to further assess real-world cost-effectiveness of TNF-therapy.