OBJECTIVES: Biologic agents are commonly used sequentially to treat moderate to severe rheumatoid arthritis (RA). In absence of clinical trials comparing biologic strategies, simulation models are useful to inform decisions. The objective is to assess, using the NHS perspective, the cost-effectiveness of biologic strategies in patients with an insufficient response (IR) to at least 1 anti-TNF agent. METHODS: Simulation models were developed to assess four strategies of different biologic agents over 2 years. Assuming an IR to the 1st anti-TNF agent, Sequence 1 included etanercept-abatacept-adalimumab and Sequence 2 etanercept-rituximab-adalimumab. Assuming an IR to 2 anti-TNF agents, Sequence 3 included etanercept-adalimumab-abatacept and Sequence 4 etanercept-adalimumab-infliximab. Effectiveness data was derived from published evidence based on achieving a low disease activity state (LDAS).  Switch occurred at each 6 months in case of an IR to the previous agent. UK direct medical costs and biologic drug costs were used.  Extensive probabilistic sensitivity analyses were performed. RESULTS: There were 6-month medical costs (excluding biologic drug costs) were estimated at £1047 (Standard Deviation [SD] 332) for managing patients in LDAS and at £2650 (SD 963) for moderate-to-high disease activity. Over 2 years, Sequence 1 appeared more efficacious (92 days in LDAS) versus Sequence 2 (82 days in LDAS,) with cost-effectiveness ratios of £281/day in LDAS vs. £289/day in LDAS, respectively. Sequence 3 appeared more efficacious (43 days in LDAS or) vs. Sequence 4 (32 days in LDAS), with cost-effectiveness ratios of £603/day in LDAS vs. £809/day in LDAS, respectively. CONCLUSIONS: Medical costs associated with moderate-to-high disease activity are estimated to be 2.5 times higher than for LDAS, suggesting that efficacious treatment strategies contribute to reducing use of health care services. The results of this simulation model suggest that, for achieving LDAS, sequences including abatacept after an IR to at least 1 anti-TNF agent appear more cost-effective than similar sequences including rtx or cycled anti-TNF agents.