AB0633 DO JANUS KINASE INHIBITORS LEAD TO WEIGHT GAIN IN RHEUMATOID ARTHRITIS PATIENTS?
Authors: S. Venkatachalam, N. Mir, N. Naina, H. Muhammed, G. Hirsch, T. Sheeran
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Janus kinase (JAK) inhibitors are promising drugs in the treatment of various autoimmune rheumatic disorders. While the clinical efficacy of JAK inhibitors is well-documented, an intriguing and clinically significant aspect the potential association between JAK inhibitors and weight gain is being reported. Weight gain holds relevance not only for patients' quality of life but also for its potential impact on treatment adherence and overall health outcomes. Several preclinical studies have provided insights into the mechanisms through which JAK inhibitors may influence weight regulation. These mechanisms encompass direct effects on adipose tissue, modulation of metabolic pathways, and interference with key signalling molecules involved in energy homeostasis. For instance, JAK inhibitors have been implicated in altering leptin signalling, a hormone crucial for appetite regulation and energy balance. <h3>Objectives:</h3> We aimed to investigate the changes in weight in rheumatoid arthritis (RA) patients treated with JAK inhibitors and the factors associated with it. <h3>Methods:</h3> We conducted a retrospective analysis of RA patients initiated on JAK inhibitors between January 2018 and December 2022 in a regional rheumatology unit in the United Kingdom. Demographic information, disease activity measures, concurrent DMARDs, steroid use, and comorbidities were collected besides the weight recorded at each clinic visit for up to 24 months. Percentage change in weight at 9-12 months was calculated for each group. Linear mixed-effects models were developed for change in weight gain considering various factors which could be implicated. To visualize the weight trajectory, LOESS (Locally Weighted Scatterplot Smoothing) plots were generated. All statistical analysis and data visualisations were done using R studio (v 2023). <h3>Results:</h3> We had 230 patients on Baricitinib and 45 on Tofacitinib for RA. Majority were females (78.5%) and the mean age was 59.4 ± 12.2 years. The mean baseline Disease Activity Score 28 (DAS28) was 5.9 ± 0.9, and a majority of patients were seropositive for rheumatoid factor (56.1%) and/or anti-cyclic citrullinated peptide antibodies (70.5%). Concomitant medications included methotrexate (43.5%), hydroxychloroquine (18.5%), and steroids (10.3%). The mean baseline weight was 76.2 ± 20.1 kg. Weight at baseline and 9-12 months were available for 157 patients. One-third of patients exhibited a weight gain exceeding 5% at 9-12 months (32.2%). Six (4.4%) in baricitinib group had a weight gain greater than 15%. The linear mixed-effects model revealed a statistically significant, increase in weight among patients on Baricitinib (p-value &lt; 0.001). Notably, concomitant methotrexate use was associated with a reduced risk of weight gain in baricitinib group (p-value = 0.008). However, the linear mixed-effects model did not identify a statistically significant change in weight among patients receiving Tofacitinib. <h3>Conclusion:</h3> Weight gain is associated with JAK inhibitor treatment in this study. Concomitant Methotrexate decreased risk of weight gain associated with Baricitinib. Further research is warranted to delineate the specific pathways and factors contributing to weight changes in individuals undergoing JAK inhibitor therapy. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>