OBJECTIVES: The management of moderate to severe rheumatoid arthritis includes the use of biologic agents. Modelling allows simulation of complex biologic treatment strategies after an insufficient response (IR) to previous biologic agents. The objective is to assess the cost-effectiveness of various biologic treatment sequences over two years according to the Turkish health care system using a public payer perspective. METHODS: Six treatment strategies using three successive biologic agents [etanercept (ETA), adalimumab (ADA), infliximab (INF), abatacept ( ABA) or rituximab (RTX)], were modelled based on Turkish medical practice. Effectiveness was derived from published evidence as expected number of days in low disease activity state (LDAS). Biologic treatment was maintained for achieving LDAS or switched at each six months in case of IR.  Total medical costs were estimated per level of disease activity over 6 months.  Extensive probabilistic sensitivity analysis was performed. RESULTS: Considering an IR to 1 anti-TNF agent, the sequence ETA-ABA-ADA was more efficacious and cost-effective (102 days in LDAS; 496 TL per day in LDAS) over 2 years than the sequence ETA-RTX-ADA (82 days in LDAS; 554 TL per day in LDAS or 81 days in LDAS; 563 TL / day in LDAS based on RTX current reimbursement status). Considering an IR after 2 anti-TNF agents, the sequences ETA-ADA-ABA and ETA-INF-ABA were more efficacious and cost-effective (64 days in LDAS for both; 841 and 826 TL / day in LDAS, respectively) over 2 years than a sequence of anti-TNF agents only (32 days in LDAS; 1480 TL per day in LDAS). CONCLUSIONS: These simulations suggest that over two years of therapy, sequences including abatacept after an IR to one anti-TNF agent are more efficacious and cost-effective vs. similar sequences including rituximab. Sequences including abatacept after an IR to 2 anti-TNF agents also appear more effective and cost-effective than similar sequences composed of anti-TNF agents only.