SAT0170 Anti-il-6 therapy modulates leptin in patients with rheumatoid arthritis

Background: Leptin is an adipocytokine that plays an important role in the regulation of body weight and also participates both in immune homeostasis and inflammatory processes [1,2]. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA) [3]. IL-6 blocker yields a rapid improvement of endothelial function [4]. Objectives: To determine whether the infusion of IL-6 blockade improves the endothelial function by altering circulating Leptin concentrations in patients with RA. Methods: 50 Spanish patients on treatment with anti-IL-6 monoclonal antibody-Tocilizumab who fulfilled the 2010 classification criteria for RA [5] were recruited. Patients with diabetes mellitus or plasma glucose >110 mg/dl were excluded. Leptin serum levels were determined immediately prior to (time 0) and after (time 60 minutes) Tocilizumab infusion by Enzyme-Linked ImmunoSorbent Assay (ELISA). Results: A significant reduction in Leptin concentration was observed following Tocilizumab infusion (mean±standard deviation (SD): 9.24±7.98 ng/ml versus 7.91±7.36 ng/ml, px0.0011). In addition, a significant positive correlation between Leptin concentration and insulin resistance (HOMA at the time of the study) was found (r= 0.40; p=0.0046). Furthermore, a significant negative correlation between Leptin levels and insulin sensitivity (QUICKI) was disclosed (r= -0.46; p=0.0009). Conclusions: Our study confirms that circulating Leptin concentrations are modulated by anti-IL-6 treatment. In addition, Leptin concentration correlates with insulin resistance and sensitivity. The beneficial effect of anti-IL-6 blockage on cardiovascular mortality in RA may be mediated by reduction in serum levels of leptin. References 1] Nat Rev Immunol2006;6:772–83. 2] Nat Rev Immunol2006;6:772–83. 3] Autoimmun Rev2016;15:1013–30. 4] Atherosclerosis2011;219:734–6. 5] Arthritis Rheum2010;62:2569–81. Acknowledgements: This study was supported by European Union FEDER funds and “Fondo de Investigacion Sanitaria” (PI15/00525) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Program RD16/0012 (RIER) from the ISCIII, and in part by grants from the European IMI BTCure Program. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, “Investing in your future”) (CP16/00033). FG is a recipient of a Sara Borrell post-doctoral fellowship from the ISCIII, co-funded by ESF (CD15/00095). SR-M is supported by funds of the RETICS Program (RIER) RD16/0012/0009 (ISCIII, co-funded by the European Regional Development Fund, ERDF). VM is supported by funds of a Miguel Servet type I programme (CP16/00033) (ISCIII, co-funded by ERDF). Disclosure of Interest: None declared