OBJECTIVES: Systemic Lupus Erythematosus (SLE) is a chronic non-organ specific autoimmune disease and is characterized by a dysregulation of the immune system that involves many organs and systems. It affects about 28,500 people in Italy, especially women of childbearing age (female-male ratio 9:1) that may have a compromised functional state and a decreased quality of life. The purpose of this analysis is to determine the cost-effectiveness of belimumab, a new biological treatment specifically developed for the treatment of SLE, in the Italian setting. METHODS: A cost-effectiveness micro simulation model with a lifetime horizon was adapted to the Italian setting. The analysis compares the standard of care (SoC) alone vs belimumab plus SoC from the perspective of the National Healthcare System. Clinical-economic consequences of the therapy and of the development of organ damage were calculated. When available, Italian data were used, otherwise UK costs were transformed into euros using the purchasing-power parity approach. The utility values were based on the EQ-5D of belimumab clinical trials (BLISS 52 and 76). The results were discounted by 3% for both costs and effects. It was considered a duration of treatment with belimumab of 6 years and it was assumed that the drug is used with wastage. RESULTS: The results of the cost-effective analysis in terms of cost per life year gained (ICER) and cost per QALY (ICUR) were € 22,990 and € 32,859 respectively. These values drop to € 20,119 and € 28,754 respectively when indirect costs are included. CONCLUSIONS: In this analysis, the results of ICER and ICUR show that belimumab is cost-effective in the Italian setting, according to the guidelines of the Italian Association of Health Economics (€ 25-40,000/QALY).