Anti-IL-6 Therapy Modulates Leptin in Patients with Rheumatoid Arthritis

Sara Remuzgo-Martínez¹, Fernanda Genre¹, Verónica Pulito-Cueto¹, Verónica Mijares¹, Leticia Lera-Gómez¹, Jaime Calvo-Alén², Ricardo Blanco¹, Oreste Gualillo³, Javier Llorca⁴, Santos Castañeda⁵, Raquel Lopez-Mejías¹ and Miguel Angel González-Gay^1,6,7, ¹Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain, Santander, Spain, ²Rheumatology Department, Hospital Universitario Araba. Vitoria-Gasteiz, Alava, Spain, ³SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Santiago de Compostela, Spain, Santiago de Compostela, Spain, ⁴Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, Spain, Santander, Spain, ⁵Hospital Universitario La Princesa, IIS-Princesa, Madrid, Spain, ⁶Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, ⁷School of Medicine, University of Cantabria, Santander, Spain, Santander, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Biomarkers, Cardiovascular disease and rheumatoid arthritis (RA), IL-6

Session Information

Date: Monday, October 22, 2018

Title: Rheumatoid Arthritis – Treatments Poster II: PROs, Safety and Comorbidity

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Leptin is an adipokine that plays an important role in the regulation of body weight and also participates 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 function⁴.Therefore, the aim of this study was 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 RA⁵ 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 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, p˂0.0011). 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).

Conclusion: 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 Immunol 2006; 6: 772-83. [2] Nat Rev Immunol 2006; 6: 772-83. [3] Autoimmun Rev 2016; 15: 1013-30. [4] Atherosclerosis 2011; 219: 734-6. [5] Arthritis Rheum 2010; 62: 2569-81.

FG is a recipient of a Sara Borrell fellowship (ISCIII, co-funded by ESF (CD15/00095). RL-M is a recipient of a Miguel Servet type I programme fellowship (ISCIII, co-funded by the European Social Fund –ESF-, “Investing in your future”)(CP16/00033). SR-M is supported by funds of the RETICS Program (RIER) RD16/0012/0009 (ISCIII, co-funded by the European Regional Development Fund, ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (CP16/00033) (ISCIII, co-funded by ERDF).

Disclosure: S. Remuzgo-Martínez, None; F. Genre, None; V. Pulito-Cueto, None; V. Mijares, None; L. Lera-Gómez, None; J. Calvo-Alén, None; R. Blanco, None; O. Gualillo, None; J. Llorca, None; S. Castañeda, None; R. Lopez-Mejías, None; M. A. González-Gay, None.

To cite this abstract in AMA style:

Remuzgo-Martínez S, Genre F, Pulito-Cueto V, Mijares V, Lera-Gómez L, Calvo-Alén J, Blanco R, Gualillo O, Llorca J, Castañeda S, Lopez-Mejías R, González-Gay MA. Anti-IL-6 Therapy Modulates Leptin in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/anti-il-6-therapy-modulates-leptin-in-patients-with-rheumatoid-arthritis/. Accessed .

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