Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis
Author:
Kerekes György1, Czókolyová Monika2, Hamar Attila2, Pusztai Anita2, Tajti Gábor3, Katkó Mónika4, Végh Edit2, Pethő Zsófia2, Bodnár Nóra2, Horváth Ágnes2, Soós Boglárka2, Szamosi Szilvia2, Hascsi Zsolt5, Harangi Mariann4, Hodosi Katalin2, Panyi György3, Seres Tamás6, Szűcs Gabriella2, Szekanecz Zoltán2ORCID
Affiliation:
1. Intensive Care Unit, Department of Medicine, University of Debrecen , Debrecen, Hungary 2. Department of Rheumatology, Department of Medicine, Faculty of Medicine, University of Debrecen , Debrecen, Hungary 3. Department of Biophysics and Cell Biology, Department of Medicine, Faculty of Medicine, University of Debrecen , Debrecen, Hungary 4. Division of Metabolic Diseases, Department of Medicine, Faculty of Medicine, University of Debrecen , Debrecen, Hungary 5. ScanoMed Ltd , Debrecen, Hungary 6. Department of Anesthesiology, University of Colorado Anschutz Medical Campus , Aurora, CO, USA
Abstract
Abstract
Objectives
Cardiovascular (CV) morbidity and mortality, and perpetuated synovial angiogenesis have been associated with RA. In our study we evaluated angiogenic factors in relation to vascular inflammation and function, and clinical markers in RA patients undergoing 1-year tofacitinib therapy.
Methods
Thirty RA patients treated with either 5 mg or 10 mg twice daily tofacitinib were included in a 12-month follow-up study. Eventually, 26 patients completed the study and were included in data analysis. Levels of various angiogenic cytokines (TNF-α, IL-6), growth factors [VEGF, basic fibroblast (bFGF), epidermal (EGF), placental (PlGF)], cathepsin K (CathK), CXC chemokine ligand 8 (CXCL8), galectin-3 (Gal-3) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) were determined at baseline, and at 6 and 12 months after initiating tofacitinib treatment. In order to assess flow-mediated vasodilation, common carotid intima-media thickness (ccIMT) and carotid-femoral pulse-wave velocity, ultrasonography was performed. Synovial and aortic inflammation was also assessed by 18F-fluorodeoxyglucose-PET/CT.
Results
One-year tofacitinib therapy significantly decreased IL-6, VEGF, bFGF, EGF, PlGF and CathK, while it increased Gal-3 production (P < 0.05). bFGF, PlGF and NT-proBNP levels were higher, while platelet-endothelial cell adhesion molecule 1 (PECAM-1) levels were lower in RF-seropositive patients (P < 0.05). TNF-α, bFGF and PlGF correlated with post-treatment synovial inflammation, while aortic inflammation was rather dependent on IL-6 and PECAM-1 as determined by PET/CT (P < 0.05). In the correlation analyses, NT-proBNP, CXCL8 and Cath variables correlated with ccIMT (P < 0.05).
Conclusions
Decreasing production of bFGF, PlGF or IL-6 by 1-year tofacitinib therapy potentially inhibits synovial and aortic inflammation. Although NT-proBNP, CXCL8 and CathK were associated with ccIMT, their role in RA-associated atherosclerosis needs to be further evaluated.
Funder
European Union and the State of Hungary European Social Fund National Excellence Program European Union
Publisher
Oxford University Press (OUP)
Subject
Pharmacology (medical),Rheumatology
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