Effects of Tofacitinib Therapy on Angiogenic Biomarkers in Rheumatoid Arthritis
Rheumatoid arthritis is a chronic inflammatory disorder that affects not only the joints but can also damage other parts of the body including the skin, lungs (1), heart and blood vessels. Patients with RA have a notable 50-70% increased risk of developing cardiovascular diseases compared to the general population (2).
Effects of Tofacitinib Therapy on Angiogenic Biomarkers in Rheumatoid Arthritis
In a recent study, highlighting the Biomedica NT-proBNP ELISA Kit*, researchers investigated for the first time the effects of 1-year Tofacitinib therapy on angiogenic biomarkers in relation to vascular inflammation and function as well as clinical markers in patients with rheumatoid arthritis (RA) (3). Tofacitinib is a medication used to treat RA. It inhibits Janus kinase enzymes which are involved in cytokine signaling leading to inflammation and symptoms of RA (4).
*Serum NT-proBNP (pmol/l) concentrations were detected by commercially available ELISA kits (NT-proBNP ELISA, Biomedica, Vienna, Austria)
NT-proBNP ELISA Kit (cat. no. SK-1204)
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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.
Literature
- Identification, Monitoring, and Management of Rheumatoid Arthritis-Associated Interstitial Lung Disease. Koduri G and Solomon JJ. Arthritis Rheumatol, 2023; Dec;75(12):2067-2077. doi: 10.1002/art.42640.
- Association of cardiovascular risks in rheumatoid arthritis patients: Management, treatment and future perspectives. Nishant Johri et al., 2023; Health Sciences Review, Vol 8.
- Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis. Kerekes G et al., Rheumatology (Oxford), 2023; 62(SI3):SI304-SI312. doi: 10.1093/rheumatology/kead502.
- Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician. Szekanecz Z et al., Nat Rev Rheumatol, 2024; 20(2):101-115. doi: 10.1038/s41584-023-01062-9.