OBJECTIVES: Rituximab (MabThera™) selectively targets B cells and represents an effective therapeutic approach for RA in addition to existing treatments, such as disease-modifying anti-rheumatic drugs (DMARDs) and tumour necrosis factor (TNF) inhibitors. This study explores the cost-effectiveness of rituximab in TNF-IR patients in the Netherlands. METHODS: The analysis reflects efficacy of the compared strategies based on two parameters: ACR response and HAQ score. A network meta-analysis provided evidence on the comparative efficacy of treatments based on ACR response. Evidence from the REFLEX trial and secondary sources are used to project HAQ score changes of patients over time. Cost input for the analysis is derived from local sources in the Netherlands. Utility data (EQ-5D) from a patient registry is analysed and categorised into six HAQ score bands based on disease severity. All input is synthesised through an individual simulation model that compares three treatment strategies after failure of a first TNF: one sequence containing rituximab, one containing TNF (i.e. TNF-cycling) and one containing abatecept. Uncertainty around model parameters is explored through probabilistic sensitivity analysis. A scenario analysis uses data on loss of productivity to estimate the indirect costs of the comparing strategies. RESULTS: In the base-case analysis, the strategy with rituximab dominates the other strategies. The result is the same in probabilistic sensitivity analysis where over 98% of the samples show that the sequence with rituximab dominates both other strategies. CONCLUSIONS: The addition of rituximab +MTX in the standard of care of patients with inadequate response to TNF treatment is estimated to be a cost-effective strategy.