Background:In recent years, the relationship between obesity and autoimmune diseases has taken interest, since adipose tissue has been identified as an endocrine organ that secretes cytokines (adipokines), among which leptin stands out as a soluble pro-inflammatory mediator associated with the body mass index (BMI).Objectives:The main objectives of this study are: i) to analyse the influence of BMI on clinical response in Rheumatoid Arthritis (RA) patients who initiate TNF-inhibitor (TNFi) therapy; ii) to analyse the differences in the serum profile of adipokines (leptin and adiponectin) according to BMI and their association with response to treatment.Methods:Observational study of a prospective cohort of 73 RA patients who initiated biological treatment with TNFi from the Complex Therapy Unit (CTU) of our Hospital. Patients were classified according to their BMI in normal-weight (BMI<25) and overweight/obesity (O/O) (IMC≥25). Demographic, clinical and laboratory variables were collected at baseline and at 6 months. Our outcome measures were DAS28-VSG remission (DAS28<2.6) at 6 months after TNFi initiation. Serum leptin and adiponectin levels were measured by Enzyme-Linked Immuno Sorbent Assay (ELISA) at baseline and 6 months. A descriptive sample analysis comparing the characteristics of both patient subgroups was performed using Chi-square, T-test for independent samples and U-Mann Whitney. Likewise, a bivariate analysis was carried out by means of binary logistic regression to assess the probable association of the parameters studied with remission.Results:Of the 73 patients studied, 51% were classified in O/O group. The O/O patients presented higher levels of baseline CRP (16.69±6.16 vs 8.74±3.81, p=0.01). No statistically significant differences were observed in the remaining variables (sex, age at the beginning of the TNFi, disease duration, baseline DAS-28), as well as therapeutic variables (use of previous DMARDs and doses of methotrexate and/or steroids). Patients with overweight/obesity presented higher DAS28-ESR values at 6 months of treatment (3.59±1.14 vs 2.93±1.27, p=0.02) and achieved remission less frequently (18.9% vs 48.6%, p=0.007). Serum leptin levels were significantly higher in O/O patients, both baseline (29.39±21.50 vs 13.49±8.78, p<0.001) and 6 months (33.06±22.03 vs 14.77±9.50, p<0.001) after TNFi initiation. In addition, O/O patients were less likely to reach remission at 6 months than normal-weight patients. [OR= 4.04 IC95% (1.40-11.64); p=0.009]. Lower frequency of remission was associated to greater leptin levels at 6 months [OR=0.94 CI95% (0.90-098); p=0.012]. No differences in serum adiponectin were found between both subgroups of patients.Conclusion:In this RA patient cohort, overweight/obesity is associated with i) a reduced response to TNFi therapy and ii) a lower short-term remission rate. Within the adipokine profile, leptin seems to play a relevant role in the maintenance of pro-inflammatory activity with a negative influence on the response to TNFi therapy in O/O patients.References:[1] Versini M. et al. Autoimmun Rev. 2014; 13, 981-1000[2] Toussirot E et al. Life Sci. 2015;140: 29-36.Disclosure of Interests:Marta Novella-Navarro: None declared, Borja Hernández-Breijo: None declared, Fernanda Genre: None declared, Leticia Lera-Gómez: None declared, Verónica Pulito-Cueto: None declared, Laura Nuño: None declared, Alejandro Villalba: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Chamaida Plasencia: None declared
Re-evaluation of serum leptin and adiponectin concentrations normalized by body fat mass in patients with rheumatoid arthritis