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. 2025 Feb 27;17(5):820.
doi: 10.3390/nu17050820.

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

Marta Novella-Navarro  1   2 , Ana Van Den Rym  3 , Chary López-Pedrera  4 , Ana Martínez-Feito  5 , Beatriz Nieto-Carvalhal  2 , Keren Reche  6 , Clementina López-Medina  4 , Alejandro Escudero-Contreras  4 , Pilar Nozal  5 , Maria Eugenia Miranda-Carús  1   2 , Irene Monjo  1   2 , Eugenio De Miguel  1   2 , Alejandro Balsa  1   2 , Rebeca Pérez-De Diego  3 , Chamaida Plasencia-Rodríguez  1   2
Affiliations

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

Marta Novella-Navarro et al. Nutrients. .

Abstract

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.

Keywords: adipose tissue cytokines; obesity; rheumatoid arthritis; targeted synthetic disease-modifying antirheumatic drugs.

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Conflict of interest statement

M. Novella-Navarro reports grants from Alfasigma, UCB pharma, Abbvie and Lilly outside the submitted work. Ch. Plasencia-Rodriguez reports grants from Abbvie, Pfizer, Novartis, Lilly and Roche outside the submitted work. E. De Miguel reports grants from Abbvie, Novartis, Roche, Pfizzer, Janssen, Lilly, MSD, BMS, UCB, Grunhental and Sanofi outside the submitted work. IM reports grants from Roche, Novartis, UCB, Janssen, Alfasigma and Gedeon Richter outside the submitted work. The other authors have declared no competing interests.

Figures

Figure 1
Figure 1
Correlation between BMI and leptin levels at baseline and 6 months after JAKi initiation.
Figure 2
Figure 2
Correlation between BMI and adiponectin levels at baseline and 6 months after JAKi initiation.
Figure 3
Figure 3
Correlation between BMI and disease activity measured by CDAI and DAS28.
Figure 4
Figure 4
Serum leptin/adiponectin levels at baseline and 6 months divided according to response to treatment.
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