OBJECTIVES: Rheumatoid Arthritis (RA) is a chronic, inflammatory disease affecting 0.68% of the adult population in Greece. RA is associated with a lowered quality of life and a serious economic burden. This study aims to evaluate the cost-effectiveness of adding tocilizumab to a treatment sequence for patients with active RA, who had an inadequate response to one or more traditional disease-modifying antirheumatic drugs (tDMARDs) and are intolerant or contraindicated to methotrexate (MTX). METHODS: A patient-level simulation model was applied to project lifetime costs and outcomes for 10.000 patients from a payer’s perspective. The analysis compared a standard treatment pathway (STP) (adalimumab, etanercept and palliative care) with a similar pathway initialized with tocilizumab (TCZ). Disease severity was reflected by Health Assessment Questionnaire (HAQ) scores. As primary efficacy outcomes, American College of Rheumatology (ACR) response rates were used. Patient characteristics (age, gender and baseline HAQ score) and TCZ efficacy data were derived from the ADACTA trial, whereas efficacy data for the remaining DMARDs were derived from a network meta-analysis of each medication’s trial outcomes. A mapping model transformed HAQ scores into QALYs. Clinical practice standards were defined by an expert panel of Greek Rheumatologists. Costs for pharmaceuticals and resource unit costs were obtained from official (Social Insurance) price lists. A discount rate of 3% was used for both costs and QALYs. RESULTS: Results indicate that a treatment sequence starting with TCZ yields 1.17 more QALYs (9.38 vs. 8.21) for an additional cost of €33,145 (€125,409 vs. €92,264) compared to the STP. The Incremental Cost – Effectiveness Ratio (ICER) was 28,325.5€/QALY gained. Sensitivity Analysis confirms robustness of findings below a threshold of €45.000. CONCLUSIONS: The results of the analysis suggest that TCZ as a first-line biologic drug can be a cost-effective treatment option for the management of active RA in patients intolerant or contraindicated to MTX.