OBJECTIVES: To evaluate the cost-utility of CZP compared with standard-of-care first-line administered TNF-inhibitors + MTX in the treatment of moderate-to-severe RA in Spain. METHODS: A Markov (cohort health state transition) model was developed to evaluate the cost-utility of CZP versus the other TNF-inhibitors licensed and recommended in Spain (etanercept [ETA], adalimumab [ADA], and infliximab [IFX]). Treatment efficacy was measured using ACR-responses (ACR20, ACR50 or ACR70) at 6 months. ACR estimated response rates were based on adjusted indirect comparison (MTX as the common comparator) of published clinical trials. Utilities were derived from EQ-5D data collected in CZP RA clinical trials. Clinical history and resource use data came from published literature. Unit costs (drug, administration, monitoring, and resources) were taken from Spanish routine sources or published references (cost year 2009). Base case analysis was conducted from the payer perspective, with a lifetime horizon, annual discounting rates of costs and outcomes of 3.5% and inflation rate for 2009 onwards of 3%. One-way sensitivity analyses were conducted. RESULTS: The average lifetime costs for CZP+MTX, ETA+MTX, ADA+MTX and IFX+MTX were €140,971, €141,197, €139,148 and €136,961, respectively. The quality-adjusted life-years (QALYs) gained were 6.578, 6.462, 6.430 and 6.318, respectively. The deterministic cost-effectiveness analysis found that CZP+MTX dominated ETA+MTX (lower cost, greater QALYs), and that CZP+MTX was cost-effective vs ADA+MTX and IFX+MTX at the €30,000/QALY willingness-to-pay threshold (ICERs of €12,346/QALY and €15,414/QALY, respectively). One-way sensitivity analyses showed that ICERs were most sensitive to the change in annual discount rates, the model cycle (evaluation of ACR response at 3 instead of 6 months), the analysis perspective and the estimation of utilities (HAQ-DI mapping instead of direct evaluation from EQ-5D). CONCLUSIONS: This analysis shows that CZP+MTX is cost-effective versus the other considered TNF-inhibitors recommended in Spain for the treatment of RA.