OBJECTIVES: Rituximab (RTX; MabThera), a unique B-cell therapy, is a new option for rheumatoid arthritis (RA) patients who respond inadequately to anti-TNF therapies. This analysis evaluated the cost-effectiveness of introducing RTX from the perspective of the UK NHS. METHODS: The model simulated, over a patient's expected lifetime, the real-life treatment sequence for 10,000 RA patients who respond inadequately to one anti-TNF therapy. Baseline characteristics were aligned with the REFLEX study. Clinical outcomes were based upon ACR response rates (adjusted for different study populations) and complemented with observational data. The model estimated the incremental cost per quality-adjusted life-year (QALY) of a typical treatment sequence containing RTX compared to the same treatment sequence without RTX. Average time-on-treatment for biological agents was up to 4.25 years. QALYs were mapped from a disease severity measure (HAQ score). All direct NHS costs were included in the model, as well as those related to disease progression and palliative care. Costs and benefits were discounted at 3.5%. RESULTS: The annual average drug cost for each drug in the model was BRP5,834 for RTX + MTX (infusion of 2x1 gram every 9 months), BRP10,138 for adalimumab, BRP10,279 for etanercept, and BRP8,542 for infliximab. The model estimated that when added to an existing treatment sequence, RTX would lead to a gain of 0.526 QALYs at an additional cost of BRP7,417 per patient. The incremental cost-effectiveness ratio (ICER) of RTX was consequently BRP14,122. When RTX replaced adalimumab as a second-line biologic DMARD, RTX + MTX was associated with a cost-saving of BRP13,000 over a patient's lifetime. CONCLUSIONS: RTX as a treatment option for RA patients who fail to respond to anti-TNF therapy is a cost effective treatment option from the perspective of the UK NHS. The resulting cost effectiveness ratio falls well below commonly accepted thresholds within the UK.