OBJECTIVES: Biologic therapy constitutes the current mainstay of rheumatoid arthritis (RA) patients treatment who have inadequately responded to methotrexate (MTX-IR). The objective of this study was to compare the relative efficacy, safety and tolerability of abatacept subcutaneous (sc) vs. all relevant comparators in MTX-IR patients with RA. METHODS: A systematic literature review identified clinical trials investigating the efficacy, safety and tolerability of abatacept intravenous and sc, adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and anakinra in combination with MTX. The efficacy endpoints were:  Health Assessment Questionnaire (HAQ) change from baseline (CFB), American College of Rheumatology (ACR) 20/50/70 response rates, and Disease activity score 28 joints (DAS28) remission rates defined as DAS28≤2.6, after 24 and 52 weeks of treatment. Safety and tolerability endpoints were:  incidence of serious adverse events (AE), infections, serious infections, withdrawals for any reason, due to AE or due to lack of efficacy. Results were analysed using indirect treatment comparison methods estimating the expected relative effect of treatments, and were expressed as the difference in HAQ CFB and the Risk Ratio of achieving an outcome and associated 95% Credible Intervals. RESULTS: The analysis of HAQ CFB showed that abatacept sc is expected to show a relative efficacy comparable to other biologic. Furthermore, abatacept sc showed ACR20/50/70 response rates and DAS28 remission rates comparable to other biologic treatments at both time periods. Abatacept sc is expected to show a comparable safety and tolerability to other biologic treatments, having a similar incidence of serious AE, infections, serious infections, withdrawals for any reason, due to AE or due to lack of efficacy. CONCLUSIONS: Considering the assumptions of a NMA, abatacept sc is expected to produce similar HAQ CFB, ACR20/50/70 and DAS28 rates and a similar incidence of serious AE, infections, serious infections and withdrawals compared to other biologics in MTX-IR RA patients.