AB0225 INCREASED HOMOCYSTEINE LEVELS DURING THE FIRST 3 MONTHS OF BARICITINIB THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Felis-Giemza, K. Chmurzyńska, M. Ciechomska, P. Klimek, W. Maśliński, M. Massalska
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with rheumatoid arthritis (RA) are at increased risk of venous thromboembolism (VTE) compared with the general population and correlation with disease activity has been shown. Even if remission is achieved, the risk of VTE is still increased [1]. There are published reports about Janus kinase inhibitors (JAKi) being connected with additional VTE risk, with baricitinib (BARI) carrying the highest risk among them [2]. Correlation between homocysteine (HCY) concentration and RA activity has been described [3]. With hyperhomocysteinemia being known an independent risk factor for atherosclerotic cardiovascular disease, it has been discussed as a potential reason for increased thrombotic risk in RA patients [3]. <h3>Objectives:</h3> We aimed to assess HCY levels in patients with active RA in the early period of baricitinib treatment. <h3>Methods:</h3> A total of 18 RA patients with high disease activity (DAS28 &gt;5.1), the inefficacy of at least one conventional DMARD, and without a history of cardiac event or VTE were qualified for BARI therapy. HCY, D-dimer (DD), ESR, and CRP were measured before introducing baricitinib (4 mg daily) and 3 months after starting the therapy in RA subjects. Disease activity and the occurrence of VTE up to 6 months were reported. HCY concentrations were also obtained from 20 healthy controls (HC). The study was approved by the local Ethics Committee. <h3>Results:</h3> Of 18 RA patients, 94% were female with a mean age 51.9±3.0 years. 13 patients received BARI - combo (BARI + methotrexate with folate supplementation) and 5 BARI monotherapy. Baseline HCY levels in RA patients were numerically higher than in HC (9.1±0.5 µmol/l vs 8.5±0.4 µmol/l, ns). After 3 months of the treatment, all patients have responded to baricitinib therapy: DAS-28 decreased from 5.8±0.2 to 3.6±0.2 (p&lt;0.0001), but HCY concentrations in those patients increased significantly from 9.1±0.5 µmol/l to 10.7±0.6 µmol/l (p=0.018). HCY did not correlate with disease activity measured by DAS-28. DAS-28 positively correlated with DD, ESR and CRP before treatment. All patients continued therapy up to 6-month and no VTE was reported in this period. <h3>Conclusion:</h3> Elevation in HCY level at month 3, despite decreased disease activity, needs further investigation. Baricitinib therapy in RA patients was effective in the early period in the means of disease activity and safe in the means of VTE risk. <h3>REFERENCES:</h3> [1] Molander V, Bower H, Frisell T, Askling J. Risk of venous thromboembolism in rheumatoid arthritis, and its association with disease activity: a nationwide cohort study from Sweden. <i>Ann Rheum Dis</i>. 2021;80(2):169-175. doi:10.1136/annrheumdis-2020-218419. [2] Xie W, Huang Y, Xiao S, Sun X, Fan Y, Zhang Z. Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials. <i>Ann Rheum Dis</i>. 2019;78(8):1048-1054. doi:10.1136/annrheumdis-2018-214846. [3] Popescu D, Rezus E, Badescu MC, et al. Cardiovascular Risk Assessment in Rheumatoid Arthritis: Accelerated Atherosclerosis, New Biomarkers, and the Effects of Biological Therapy. <i>Life (Basel</i>). 2023;13(2):319. Published 2023 Jan 23. doi:10.3390/life13020319. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>