OBJECTIVES: Analyze Tocilizumab (TCZ) monotherapy cost-utility for moderate/severe rheumatoid arthritis in patients who are intolerant/contraindicated to MTX, compared with two standard treatment sequences: comparison 1: Etanercept-Adalimumab-Certolizumab-Support treatment vs. Tocilizumab-Etanercept-Adalimumab-Support treatment, and comparison 2: Adalimumab-Etanercept-Certolizumab- Support treatment vs. Tocilizumab-Adalimumab-Etanercept-Support treatment. METHODS: A life time micro-simulation model with 6 months cycles was performed in order to calculate the incremental cost-effectiveness ratio of the TCZ treatment sequences vs. standards sequences, which were determined by an expert panel of Spanish rheumatologists. Demographic data on age, HAQ score and sex were obtained from the ADACTA trial, while body weight data was obtained from the PRAXIS study. The efficacy data (ACR clinical response) were obtained from the pivotal clinical trial of each drug. Utilities were calculated from the relationship between ACR response, HAQ score and EQ5D instrument, according to the VACAR study, conducted in the Spanish population. The analysis was done from National Health System (NHS) perspective. Unit costs (€; 2012) were obtained from Spanish sources. Annual discount rate was 3.5% for costs and outcomes. Probabilistic sensitivity analyses were performed. RESULTS: TCZ sequences generated more costs per patient than the standard sequence (€ 7,107 in comparison 1; € 6,087 in comparison 2). However, the TCZ sequence generated more QALYs than the standard sequence (0.330 in comparison 1 and 0.297 in comparison 2). The cost of gaining a QALY with TCZ sequences versus the standard sequence was € 21,529 (comparison 1) and € 20,496 (comparison 2). According to probabilistic sensitivity analyses, the probability that the TCZ sequences are cost effective is 86.8% for the comparison 1 and 86.1% for the comparison 2. CONCLUSIONS: In both comparisons, the analysis results indicate that the inclusion of TCZ monotherapy as first-line represents an effective and cost-effective alternative in Spain versus the current sequences used for the treatment of patients with rheumatoid arthritis and MTX intolerance/contraindication.