OBJECTIVES: To evaluate the cost-effectiveness of treatment sequences initialized with tocilizumab 8mg/kg compared to similar treatment sequences initialized with a TNF-inhibitor for the treatment of moderate to severe RA patients with inadequate response to previous DMARD therapy (DMARD-IR) in Portugal. METHODS: A cost-utility analysis was conducted from a societal perspective. The analysis compares DMARD-IR patient outcomes, in three different scenarios, in a treatment sequence initialized with tocilizumab followed by a TNF inhibitor (adalimumab, etanercept, or infliximab, for scenarios 1, 2 and 3, respectively), rituximab, abatacept and palliation versus the same sequence initialized with a TNF inhibitor (etanercept, adalimumab and etanercept, respectively, for scenarios 1, 2 and 3). Patients characteristics (age, starting HAQ-DI score, sex and weight) were based on tocilizumab clinical trial data. ACR response for biologic treatments was obtained by a mixed treatment comparison. Clinical trial data was used to model the relationship between HAQ-DI scores and utility as described by EQ-5D. Resource utilization was obtained from an expert panel of Portuguese rheumatologists. Unit costs were obtained from Portuguese official sources. Analysis of clinical trial data or secondary sources provided evidence for appropriate distributions to perform probabilistic sensitivity analysis (PSA). Costs and QALYs were discounted annually at 5%. RESULTS:   The model estimated that the treatment sequence initialized with tocilizumab resulted in higher QALYs and lower costs versus comparator sequences in all three scenarios (0.22 QALYs and -1.881€, 0.27 QALYs and -4.449€, 0.22 QALYs and -1.851€ for scenarios 1, 2 and 3 respectively). Several sensitivity and scenarios analyses showed that the model is robust to changes in parameter values. In PSA (2000 samples) the tocilizumab sequence produces always additional QALYs at lower costs.  CONCLUSIONS: In DMARD-IR patients, the model consistently predicts that starting treatment with tocilizumab is a dominant alternative compared to similar treatment sequences initialized with a TNF-inhibitor in Portugal.