THU0219 Beneficial effect of anti-il-6 blockade on insulin resistance and insulin sensitivity in patients with rheumatoid arthritis
Authors: S. Remuzgo-Martínez, R. López-Mejías, F. Genre, V. Mijares, J. Calvo-Alen, R. Blanco, J. Llorca, S. Castañeda, M.A. González-Gay
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic inflammation, insulin resistance (IR), and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA).<sup>1–3</sup> In this regard, it has been described that the blockade of IL-6, a cytokine involved in the pathogenesis of both RA and atherosclerosis, yields a rapid improvement of endothelial function in RA.<sup>4</sup> However, there are no studies on the role of anti-IL-6 treatment on IR in patients with RA. <h3>Objectives</h3> To assess whether IL-6 blockade may result in a reduction of insulin serum levels and an improvement of IR in patients with RA. <h3>Methods</h3> 50 Spanish patients on treatment with anti-IL-6 monoclonal antibody-Tocilizumab who fulfilled the 2010 classification criteria for RA<sup>5</sup> were recruited. Patients with diabetes mellitus or plasma glucose &gt;110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to (time 0) and after (time 60 min) Tocilizumab infusion. IR was assessed by the homeostasis model assessment (HOMA) and insulin sensitivity was evaluated by the quantitative insulin sensitivity check index (QUICKI). <h3>Results</h3> A marked reduction in the serum insulin levels was observed following Tocilizumab infusion (mean ±standard deviation (SD): 10.60±5.80 μU/ml versus 7.61±5.08 μU/ml, p&lt;0.0001). In addition, a decrease in the insulin/glucose index was observed in patients with RA after Tocilizumab dose (mean ±SD: 0.12±0.06 versus 0.08±0.05, p&lt;0.0001). Finally, our results disclosed a significant improvement of insulin resistance (HOMA: mean ±SD: 2.61±2.05 versus 1.65±1.14, p=0.0003) and insulin sensitivity (QUICKI: mean ±SD: 0.34±0.003 versus 0.37±0.04, p&lt;0.0001) following Tocilizumab infusion. <h3>Conclusions</h3> Our study confirms a rapid beneficial effect of Tocilizumab on IR and insulin sensitivity in RA patients treated with this drug. It may support the long-term use of drugs that act blocking IL-6 function to reduce the mechanisms implicated in the development of atherosclerosis in RA patients. <h3>References</h3> [1] Am J Med2003;114:647–652. [2] Autoimmun Rev2016;15:1013–1030. [3] Autoimmun Rev2004; 3:301–304. [4] Atherosclerosis2011;219:734–736. [5] Arthritis Rheum2010;62:2569–2581. <h3>Acknowledgements</h3> This study was supported by European Union FEDER funds and "Fondo de Investigación 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 ISCIII, and in part by grants from the European IMI BTCure Program. SR-M is supported by funds of the RETICS Program (RIER) RD16/0012/0009 (ISCIII, co-funded by the European Regional Development Fund, ERDF). 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). VM is supported by funds of a Miguel Servet type I programme (CP16/00033) (ISCIII, co-funded by ERDF). <h3>Disclosure of Interest</h3> None declared