Do Obesity and Adipose Tissue Cytokines Influence the Response to Janus Kinase Inhibitors in Rheumatoid Arthritis?

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Background: Obesity is a frequent comorbidity in rheumatoid arthritis (RA). This condition may lead these patients to have poorer disease control and a worse response to some of the available treatments. Objectives: We aim to analyze the role of body mass index (BMI) in the clinical response to Janus kinase inhibitors (JAKis) in patients with RA. We aim to perform an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels, their potential influence in disease activity and their changes with treatment. Methods: This study involved 81 patients with RA treated with JAKis from Hospital La Paz and Hospital Reina Sofía. Patients were classified according to their BMI as normal weight and overweight/obesity. The clinical response to treatment was assessed by the Clinical Disease Activity Index (CDAI) and Disease Activity Score-28 (DAS28) 6 months after the initiation of JAKis. Serum adipokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples obtained before the initiation of JAKis and after 6 months of treatment. Results: Leptin levels showed a significant positive correlation with BMI at baseline (r = 0.59, p < 0.01) and at 6 months (r = 0.56, p < 0.01) in the whole cohort, but no correlation was found between BMI and adiponectin. No correlation between disease activity and BMI was found in the whole cohort at baseline and at 6 months measured by both the CDAI and DAS28. Fifty patients (61.7%) achieved low disease activity (LDA)/remission at 6 months, regardless their BMI, and no differences in serum adipokine levels were observed at baseline and at 6 months in patients who achieved LDA vs. no-LDA. Conclusions: In this study, we did not find an association between obesity and the extent of LDA in patients treated with JAKis; therefore, this mechanism of action could be suitable for overweight/obese patients with RA.

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