OBJECTIVES: To compare the cost of using subcutaneous abatacept (SC ABA) versus other first-line biological disease-modifying antirheumatic drugs (DMARDs) available in Spain, in the treatment of patients with rheumatoid arthritis (RA) who have failed an initial treatment with methotrexate (MTX). METHODS: With regards to efficacy and safety outcomes, SC ABA was considered non-inferior vs intravenous ABA (IV ABA), adalimumab (ADA), certolizumab pegol (CZP), etanercept (ETN), golimumab (GLM), infliximab (IFX) and tocilizumab (TCZ), based on results of an indirect comparison using mixed treatment analysis. Therefore a cost- minimization analysis for a 3 year time horizon was developed. The perspective was that of the Spanish National Health System (NHS). Pharmaceutical and administration costs (€, 2013) of all biological DMARDs which are available in Spain as first-line treatment after MTX were considered. Drug costs were included in terms of ex-factory price with mandatory rebate. Administration costs were obtained from local published data. The analysis was developed for an average patient weight of 70 kg. A 3% annual discount rate was applied. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: SC ABA treatment was associated with a yearly cost of €11,521.36 per patient during the first year of treatment and €11,002.23 in subsequent years. The total 3-year cost of SC ABA was €32,138.43 per patient, proving to be cost saving versus most of the other biological DMARDs. In all cases, pharmaceutical costs lead to more than 85% of total disease management costs. Sensitivity analyses proved the model to be robust. CONCLUSIONS: According to these results, SC ABA would lead to cost-savings versus IV ABA, ADA, CZP, ETN, GLM and TZC in the management of RA patients initiating treatment with biological DMARDs.