OBJECTIVES: To evaluate the impact on Italian National Health Service (NHS) budget of the introduction of Rituximab (RTX) and Abatacept (ABAT) in the treatment of rheumatoid arthritis (RA) patients not adequately responding to anti-TNFα therapies. METHODS: First, RA patients eligible to second-line biologic treatments and the available strategies for their management were identified and quantified; second, costs associated to the different alternatives were estimated; finally, the impact on the NHS budget was estimated using a cohort simulation based on a Markov chain with 1-year cycles and a time horizon of 10 years. Only direct medical costs were considered, including drug acquisition, administration, incidental premedication and monitoring tests and exams RESULTS: Italian RA patients eligible to second-line biologic therapies were estimated in about 1,300 per year. Three strategies were identified as available: the currently used strategy, based on the switch between anti-TNFα therapies, and two innovative strategies based on RTX and on ABAT. The simulated effect of a progressive replacement (16%, 50%, and 100% at years 1, 5, and 10, respectively) of the current strategy with the two new strategies yielded the following results: RTX therapy induces a decrease of costs of 1.16 million Euro (-7.1% with respect to current strategy), 4.91 (-7.7%) and 4.94 (-5.3%) at  years 1,  5, and 10, whereas ABAT therapy induces an increase of 0.6 million Euro (+3.7%),  5.43 (+8.5%) and 20.62 (22.2%). In the direct comparison between the two new strategies RTX results less expensive (10.4%,  14.9% and 22.5% at  years 1,  5, and 10, respectively). CONCLUSIONS:The introduction of new therapies in the treatment of Italian RA patients represents a valuable option. The use of RTX is expected to induce a reduction in costs while ABAT probably would produce an increase. These results are preliminary, more detailed data on the population and observed costs are needed.