OBJECTIVES: A pharmacoeconomic analysis was performed to determine the cost implications of providing rituximab (RTX, a selective B cell therapy) + methotrexate [MTX] as an alternative for the treatment of patients with an inadequate response to anti-tumour necrosis factor [TNF] therapies in rheumatoid arthritis [RA] in the Netherlands [NL]. This analysis was performed as part of a reimbursement request. Currently RTX is reimbursed according to the Dutch Expensive Hospital Drug Act. METHODS: A cost-effectiveness model was developed to evaluate the societal costs and clinical outcomes of a standard Dutch treatment sequence either with or without RTX + MTX. The model uses Monte Carlo simulation to generate 10,000 random RA patients who start with 2nd line treatment after an inadequate response to TNF therapy + MTX. Baseline patient characteristics were taken from the RTX registration study, REFLEX. Efficacy data were taken from published literature and were placebo-adjusted to minimise bias from cross-trial comparisons. Dutch observational data were collected in order to determine local treatment patterns and resource utilisation data. Both direct and indirect medical costs were based on official price lists (2005). Costs and benefits were discounted at 4% and 1.5%, respectively. RESULTS: The average lifetime treatment costs per patient in NL were €131,531 for the current treatment sequence and €141,544 when RTX + MTX was added. QALYs gained were 3.76 for the current treatment sequence and 4.4 when RTX + MTX was added. The incremental cost-effectiveness ratio for inclusion of RTX + MTX in the current treatment sequence was €13,903/QALY. CONCLUSION: Adding RTX + MTX to the current treatment sequence is predicted to increase QALYs with a slight increase in overall lifetime costs for the society. These favourable outcomes are driven by the lower annual drug therapy costs compared with other biological alternatives.