OBJECTIVES: To assess the cost-utility and multinomial expected value of perfect information (mEVPI) of sequenced treatment with biologics in moderate-to-severe rheumatoid arthritis (msRA) after failure of traditional disease modifying antirheumatic drug(s) (tDMARD). METHODS: A probabilistic, individual sampling (microsimulation) model was developed to compare ten different treatment sequences among 3,000 hypothetical Finnish msRA patients in a lifetime scenario. Adalimumab+methotrexate (MTX), etanercept+MTX or tocilizumab+MTX were used as first biologics followed by up to three other biologics. Best supportive care including tDMARDs was assumed to be used after exhaustion of treatment options with biologics. Treatment with MTX alone was added as further comparator. The clinical outcomes (no ACR50, ACR50 and ACR70 responses conditional to the use of biologic drugs) were obtained from a recently published mixed treatment comparison and quality-adjusted life-years (QALY) were estimated based on disease severity scores (HAQ) using a nonlinear equation: EQ5D=0.82-0.11*HAQ-0.07*HAQ2. Resource use was estimated from published references and valued with Finnish unit costs (year 2009). Analyses were performed from payer perspective (productivity losses were excluded) using 3% annual discount rate. RESULTS: Compared to MTX alone, treatment with tocilizumab+MTX was more cost-effective than treatment with etanercept+MTX. Both tocilizumab+MTX and etanercept+MTX dominated adalimumab+MTX. An additional QALY gained with tocilizumab+MTX costs €15,478 (mEVPI €1,258/patient) compared with MTX alone. An additional QALY gained with tocilizumab+MTX followed by etanercept+MTX costs €35,543 (mEVPI €748/patient) compared with tocilizumab+MTX. According to cost-effectiveness acceptability frontier, only MTX alone, tocilizumab+MTX or tocilizumab+MTX followed by etanercept+MTX should be considered, if willingness to pay is €0-50,000 per QALY gained. With €30,000 per QALY gained, tocilizumab+MTX had 97.6% probability of being cost-effective. The results were relatively robust in sensitivity analyses. CONCLUSIONS: After tDMARD failure, tocilizumab+MTX or tocilizumab+MTX followed by etanercept+MTX were the most cost-effective biologics for patients with msRA. mEVPI indicated that the value of additional research information is low.