OBJECTIVES: To estimate the incremental cost-effectiveness (ICER) and cost-utility ratio (ICUR) of belimumab compared to standard care (SC) for the treatment of patients with Systemic Lupus Erythematosus (SLE) in Portugal. METHODS: A lifetime microsimulation model represented the complex and multidimensional course of SLE, based on long term data from a US cohort of SLE patients. The analysis was undertaken using a societal perspective with 5% discount rates for costs (direct and indirect costs), and effects [Life Years Gained (LYG) and QALY (Quality Adjusted Life Years)]. The model was calibrated with the phase III BLISS trials data, and UK utility values. The ICER and ICUR were estimated by comparison of SC vsSC with belimumab, with a lifetime analytic horizon. Belimumab non-responders were discontinued after 6 months and belimumab treatment was maximized at 3 years. RESULTS: The model demonstrated that adding belimumab to SC to treat SLE patients with high disease activity, positive anti-dsDNA antibodies, and low complement (C3, C4) levels, would result in a potential gain of 0.41 life-years, and  0.32 QALYs. Incremental costs were€ 8,400, resulting in an ICER of €20,649/LYG and ICUR of €25,917/QALY for the base case scenario. ICER and ICUR are insensitive to the follow-up treatment costs of SLE, and wastage of drug; moderately sensitive to duration of treatment, and waning time; and very sensitive to discount rates, and exclusion of indirect costs. The probabilistic sensitivity analysis reveals a cost-effectiveness probability of 59% for a €30,000/QALY threshold, and a median ICUR of €27,932/QALY (95% confidence interval: €14,215/QALY - €52,279/QALY). CONCLUSIONS: The analysis suggests that adding belimumab to SC for SLE patients with high disease activity, positive anti-dsDNA, and low complement levels, is cost-effective, presenting an ICER and ICUR below the commonly used threshold.  This study is funded by GlaxoSmithKline, protocol #HO-13-13626