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- Title
Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis.
- Authors
Kerekes, György; Czókolyová, Monika; Hamar, Attila; Pusztai, Anita; Tajti, Gábor; Katkó, Mónika; Végh, Edit; Pethő, Zsófia; Bodnár, Nóra; Horváth, Ágnes; Soós, Boglárka; Szamosi, Szilvia; Hascsi, Zsolt; Harangi, Mariann; Hodosi, Katalin; Panyi, György; Seres, Tamás; Szűcs, Gabriella; Szekanecz, Zoltán
- 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.
- Subjects
BIOMARKERS; CYTOKINES; BLOOD vessels; IMMUNOGLOBULINS; FIBROBLASTS; SYNOVIAL membranes; EPIDERMAL growth factor; TREATMENT duration; ANTIRHEUMATIC agents; JANUS kinases; TREATMENT effectiveness; RHEUMATOID arthritis; TUMOR necrosis factors; POSITRON emission tomography; RESEARCH funding; NEUROTRANSMITTER uptake inhibitors; VASCULAR endothelial growth factors; PEPTIDE hormones; COMPUTED tomography; VASCULITIS; LIGANDS (Biochemistry); PHARMACODYNAMICS
- Publication
Rheumatology, 2023, Vol 62, pSI304
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/kead502