Soluble vascular biomarkers in rheumatoid arthritis and ankylosing spondylitis: effects of one-year anti-TNF-α therapy

2020 ◽  
pp. jrheum.200916
Author(s):  
Anita Pusztai ◽  
Attila Hamar ◽  
Ágnes Horváth ◽  
Katalin Gulyás ◽  
Edit Végh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Oxidized Ldl ◽  
Certolizumab Pegol ◽  
Intima Media Thickness ◽  
Serum Levels ◽  
Urokinase Plasminogen Activator Receptor ◽  
Tnf Α ◽  
One Year ◽  
Vascular Biomarkers

Objective Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with cardiovascular (CV) disease. The treatment of arthritis by tumour necrosis factor α (TNF- α) inhibitors may decrease the serum concentrations of vascular biomarkers. We determined circulating levels of oxidized LDL (oxLDL)/β2 glycoprotein I (β2GPI) complexes, antibodies to 60 kDa heat shock protein (anti-Hsp60), soluble urokinase plasminogen activator receptor (suPAR) and Brain type natriuretic peptide (BNP) fragment in sera of RA and AS patients undergoing anti-TNF treatment. Methods Fifty-three RA/AS patients were treated with etanercept (ETN) or certolizumab pegol (CZP) for one year. Circulating oxLDL/β2GPI complex (AtherOx®), anti- Hsp60 IgG and BNP8-29 fragment levels were assessed by ELISA. suPAR levels were determined by suPARnostic® Quick Triage test. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) were determined by ultrasound. Results One-year anti-TNF treatment significantly decreased oxLDL/β2GPI levels, as well as suPAR levels in patients with “critically” high suPAR levels at baseline. In RA, BNP levels were higher in seropositive vs seronegative patients. Serum levels of these vascular biomarkers variably correlated with lipids, ACPA, RF and CRP. IMT positively correlated with BNP, PWV with suPAR and anti-Hsp60, while FMD inversely associated with anti-Hsp60. In RM-ANOVA analysis, disease activity supported the effects of anti-TNF treatment on 12-month changes in oxLDL/β2GPI. IMT supported the effects of therapy on changes of anti-Hsp60 and suPAR. Conclusion These biomarkers may be involved in the pathogenesis of atherosclerosis underlying RA/AS. TNF inhibition variably affect the serum levels of oxLDL/β2GPI, suPAR and BNP.

scholarly journals Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis

2019 ◽  
Vol 40 (3) ◽  
pp. 427-436 ◽  
Author(s):  
Edit Végh ◽  
György Kerekes ◽  
Anita Pusztai ◽  
Attila Hamar ◽  
Szilvia Szamosi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Vascular Function ◽  
Certolizumab Pegol ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Cardiovascular Morbidity And Mortality ◽  
Tnf Α ◽  
Flow Mediated Vasodilation

AbstractAccelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.

scholarly journals Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1535
Author(s):  
Monika Czókolyová ◽  
Anita Pusztai ◽  
Edit Végh ◽  
Ágnes Horváth ◽  
Anita Szentpéteri ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Vascular Function ◽  
Certolizumab Pegol ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Metabolic Parameters ◽  
Clinical Markers ◽  
One Year

Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

scholarly journals Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis

2019 ◽  
Vol 39 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Katalin Gulyás ◽  
Ágnes Horváth ◽  
Edit Végh ◽  
Anita Pusztai ◽  
Ágnes Szentpétery ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Ankylosing Spondylitis ◽  
Bone Loss ◽  
Bone Mineral ◽  
Certolizumab Pegol ◽  
Joint Destruction ◽  
Type I ◽  
Mineral Density ◽  
Tnf Α

Abstract Objectives Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. Patients and methods Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. Results TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP. Conclusions Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.

scholarly journals Associations of vascular and bone status in arthritis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anita Pusztai ◽  
Attila Hamar ◽  
Monika Czókolyová ◽  
Katalin Gulyás ◽  
Ágnes Horváth ◽  
...  
Keyword(s):  
Disease Activity ◽  
Certolizumab Pegol ◽  
Cathepsin K ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Quantitative Ct ◽  
Bone Status ◽  
Vascular Markers ◽  
One Year ◽  
Vascular Biomarkers

AbstractCardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

scholarly journals FRI0373 ASSOCIATIONS OF VASCULAR PATHOPHYSIOLOGY AND BONE METABOLISM IN ANTI-TNF- TREATED RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 783.2-784
Author(s):  
M. Czókolyová ◽  
K. Gulyás ◽  
Á. Horváth ◽  
E. Végh ◽  
Z. Pethö ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Certolizumab Pegol ◽  
Univariate Analysis ◽  
Inflammatory Rheumatic Diseases ◽  
Ageing Population ◽  
Research Support ◽  
Vascular Markers

Background:Cardiovascular (CV) disease and osteoporosis (OP) have become increasing challenges in the ageing population, even more in patients with inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and spondyloarthropathies. Both RA and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss, accelerated atherosclerosis, increased CV morbidity and mortality.Objectives:Bone and vascular biomarkers and parameters along with the effect of one-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS.Methods:Fifty-three patients including 36 RA patients treated with etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were assessed by ELISA. Bone density was assessed by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and pulse-wave velocity (PWV) were assessed by ultrasound. The effects of vascular markers on bone and bone effects on vasculature undergone statistical analysis.Results:Serum levels of vascular endothelial growth factor (VEGF), PDGF-BB, angiopoietin 2 (Ang2) and cathepsin K (CathK) decreased, procollagen type 1 N-propeptide (P1NP) and sclerostin (SOST) levels increased, soluble receptor activator nuclear kappa B ligand (sRANKL) and osteoprotegerin (OPG) levels showed no differences. When bone and vascular markers were correlated with each other, at baseline, OPG correlated with Ang2 and adiponectin. SOST correlated positively with ccIMT. DXA L2-4 BMD, DXA L1 BMD and DXA femoral neck (FN) BMD correlated with FMD and CRP. QCT trabecular BMD correlated with ccIMT and PON1. According to the univariate analysis, FMD correlated with OPG, ccIMT correlated with SOST and QCT trabecular BMD. Ang1, Ang2 and PDGF-BB showed correlation with Dickkopf-1 (DKK1). Ang2 also correlated with OPG. As suggested by the multivariate analysis, OPG determined FMD; DKK1 was an independent predictor of Ang1, Ang2 and PDGF-BB. OPG was a predictor of Ang2.Conclusion:In our study of anti-TNF treated RA and AS patients, vascular and bone parameters showed numerous correlations. The therapy was clinically effective, it halted further bone loss over 1 year and reduced the production of angiogenic markers.Acknowledgments:This research was supported by an investigator-initiated research grant from Pfizer.Disclosure of Interests:Monika Czókolyová: None declared, Katalin Gulyás: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Zsófia Pethö: None declared, Szilvia Szamosi: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Emese Balogh: None declared, Nóra Bodnár: None declared, Levente Bodoki: None declared, Agnes Szentpetery: None declared, Harjit Pal Bhattoa: None declared, György Kerekes: None declared, Katalin Hodosi: None declared, Andrea Domjan: None declared, Sándor Szántó: None declared, Gabriella Szücs: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen

scholarly journals Early non-response to certolizumab pegol in rheumatoid arthritis predicts treatment failure at one year. Data from a randomised phase III clinical trial

2018 ◽  
Vol 85 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Francis Berenbaum ◽  
Thao Pham ◽  
Pascal Claudepierre ◽  
Thibault de Chalus ◽  
Jean-Michel Joubert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Treatment Failure ◽  
Certolizumab Pegol ◽  
Phase Iii ◽  
Phase Iii Clinical Trial ◽  
One Year

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

2019 ◽  
Vol 64 (11) ◽  
pp. 673-676
Author(s):  
Asmaya Saftar Huseynova
Keyword(s):  
Rheumatoid Arthritis ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Hypovitaminosis D ◽  
Serum Levels ◽  
Control Group ◽  
Tnf Α ◽  
High Production ◽  
Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

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