TY - JOUR AU - Kerekes, György AU - Bodoki, Levente AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Tajti, Gábor AU - Katkó, Mónika AU - Végh, Edit AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Horváth, Ágnes AU - Soós, B. AU - Szamosi, Szilvia AU - Hascsi, Z. AU - Harangi, Mariann AU - Panyi, György AU - Szűcs, Gabriella AU - Szekanecz, Zoltán TI - AB0237 EFFECTS OF ONE-YEAR TOFACITINIB THERAPY ON ANGIOGENIC BIOMARKERS IN RHEUMATOID ARTHRITIS JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 82 PY - 2023 IS - S1 SP - 1303 EP - 1303 PG - 1 SN - 0003-4967 DO - 10.1136/annrheumdis-2023-eular.2331 UR - https://m2.mtmt.hu/api/publication/34775337 ID - 34775337 LA - English DB - MTMT ER - TY - JOUR AU - Kerekes, György AU - Czókolyová, Monika AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Tajti, Gábor AU - Katkó, Mónika AU - Végh, Edit AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Horváth, Ágnes AU - Soós, Boglárka AU - Szamosi, Szilvia AU - Hascsi, Zsolt AU - Harangi, Mariann AU - Hodosi, Katalin AU - Panyi, György AU - Seres, Tamás AU - Szűcs, Gabriella AU - Szekanecz, Zoltán TI - Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis JF - RHEUMATOLOGY (UNITED KINGDOM) J2 - RHEUMATOLOGY VL - 62 PY - 2023 IS - SI3 SP - SI304 EP - SI312 SN - 1462-0324 DO - 10.1093/rheumatology/kead502 UR - https://m2.mtmt.hu/api/publication/34215318 ID - 34215318 LA - English DB - MTMT ER - TY - JOUR AU - Kacsándi, Dorottya AU - Fagyas, Miklós AU - Horváth, Ágnes AU - Végh, Edit AU - Pusztai, Anita AU - Czókolyová, Monika AU - Soós, Boglárka AU - Szabó, Attila Ádám AU - Hamar, Attila AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Kerekes, György AU - Hodosi, Katalin AU - Szamosi, Szilvia AU - Szűcs, Gabriella AU - Papp, Zoltán AU - Szekanecz, Zoltán TI - Effect of tofacitinib therapy on angiotensin converting enzyme activity in rheumatoid arthritis JF - FRONTIERS IN MEDICINE J2 - FRONT MED VL - 10 PY - 2023 SN - 2296-858X DO - 10.3389/fmed.2023.1226760 UR - https://m2.mtmt.hu/api/publication/34185575 ID - 34185575 LA - English DB - MTMT ER - TY - JOUR AU - Soos, Boglarka AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Végh, Edit AU - Szamosi, Szilvia AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Kerekes, György AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Christians, Uwe AU - Klawitter, Jelena AU - Seres, Tamas AU - Szekanecz, Zoltán TI - Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach JF - FRONTIERS IN MEDICINE J2 - FRONT MED VL - 9 PY - 2022 PG - 16 SN - 2296-858X DO - 10.3389/fmed.2022.1011734 UR - https://m2.mtmt.hu/api/publication/33457576 ID - 33457576 N1 - Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Intensive Care Unit, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Department of Sports Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Export Date: 4 January 2023 Correspondence Address: Szekanecz, Z.; Department of Rheumatology, Hungary; email: szekanecz.zoltan@med.unideb.hu AB - IntroductionRheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA. Materials and methodsThirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points. ResultsTwenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other. ConclusionOne-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study. LA - English DB - MTMT ER - TY - JOUR AU - Czókolyová, Monika AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Tajti, Gábor AU - Végh, Edit AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Horváth, Ágnes AU - Boglárka, Soós AU - Szamosi, Szilvia AU - Szentpéteri, Anita AU - Seres, Ildikó AU - Harangi, Mariann AU - Paragh, György AU - Kerekes, György AU - Bodoki, Levente AU - Katalin, Hodosi AU - Tamás, Seres AU - Panyi, György AU - Szekanecz, Zoltán AU - Szűcs, Gabriella TI - Effects of One-Year Tofacitinib Therapy on Lipids and Adipokines in Association with Vascular Pathophysiology in Rheumatoid Arthritis JF - BIOMOLECULES J2 - BIOMOLECULES VL - 12 PY - 2022 IS - 10 SN - 2218-273X DO - 10.3390/biom12101483 UR - https://m2.mtmt.hu/api/publication/33153228 ID - 33153228 AB - Background: Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy. Patients and methods: Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment. Results: One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (p < 0.05). Regression analysis suggested, among others, association of BMI with CRP and PWV (p < 0.05). Adipokines variably correlated with age, BMI, CRP, CCP, FMD, IMT and PWV, while MPO, PON1 and TSP-1 variably correlated with age, disease duration, BMI, RF and PWV (p < 0.05). Conclusions: JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition. LA - English DB - MTMT ER - TY - JOUR AU - Soós, Boglárka AU - Fagyas, Miklós AU - Horváth, Ágnes AU - Végh, Edit AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Csongrádi, Alexandra AU - Hamar, Attila AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Kerekes, György AU - Hodosi, Katalin AU - Szekanecz, Éva AU - Szamosi, Szilvia AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Papp, Zoltán AU - Szekanecz, Zoltán TI - Angiotensin Converting Enzyme Activity in Anti-TNF-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients JF - FRONTIERS IN MEDICINE J2 - FRONT MED VL - 8 PY - 2022 SN - 2296-858X DO - 10.3389/fmed.2021.785744 UR - https://m2.mtmt.hu/api/publication/32634351 ID - 32634351 AB - Introduction: Angiotensin-converting enzyme (ACE) and ACE2 have been implicated in the regulation of vascular physiology. Elevated synovial and decreased or normal ACE or ACE2 levels have been found in rheumatoid arthritis (RA). Very little is known about the effects of tumor necrosis factor α (TNF-α) inhibition on ACE or ACE2 homeostasis. In this study, we assessed the effects of one-year anti-TNF therapy on ACE and ACE2 production in RA and ankylosing spondylitis (AS) in association with other biomarkers. Patients and Methods: Forty patients including 24 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 16 AS patients treated with ETN were included in a 12-month follow-up study. Serum ACE levels were determined by commercial ELISA, while serum ACE2 activity was assessed using a specific quenched fluorescent substrate. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. In addition, CRP, rheumatoid factor (RF) and ACPA were also measured. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy increased ACE levels in the full cohort, as well as in the RA and AS subsets. ACE2 activity increased in the full cohort, while the ACE/ACE2 ratio increased in the full cohort and in the RA subset (p < 0.05). Uni- and multivariable regression analyses determined associations between ACE or ACE/ACE2 ratios at different time points and disease duration, CRP, RF, FMD and IMT (p < 0.05). ACE2 activity correlated with CRP. The changes of ACE or ACE2 over 12 months were determined by treatment together with either RF or FMD (p < 0.05). Conclusions: Anti-TNF treatment may increase ACE and ACE2 in the sera of RA and AS patients. ACE and ACE2 may be associated with disease duration, markers of inflammation and vascular pathophysiology. The effects of TNF inhibition on ACE and ACE2 may reflect, in part, the effects of these biologics on the cardiovascular system. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, György AU - Roodenrijs, Nadia MT AU - Welsing, Paco MJ AU - Kedves, Melinda AU - Hamar, Attila AU - van der Goes, Marlies C AU - Kent, Alison AU - Bakkers, Margot AU - Pchelnikova, Polina AU - Blaas, Etienne AU - Senolt, Ladislav AU - Szekanecz, Zoltán AU - Choy, Ernest H AU - Dougados, Maxime AU - Jacobs, Johannes WG AU - Geenen, Rinie AU - Bijlsma, Johannes WJ AU - Zink, Angela AU - Aletaha, Daniel AU - Schoneveld, Leonard AU - van Riel, Piet AU - Dumas, Sophie AU - Prior, Yeliz AU - Nikiphorou, Elena AU - Ferraccioli, Gianfranco AU - Schett, Georg AU - Hyrich, Kimme L AU - Mueller-Ladner, Ulf AU - Buch, Maya H AU - McInnes, Iain B AU - van der Heijde, Désirée AU - van Laa, Jacob M TI - EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 81 PY - 2022 IS - 1 SP - 20 EP - 33 PG - 14 SN - 0003-4967 DO - 10.1136/annrheumdis-2021-220973 UR - https://m2.mtmt.hu/api/publication/32130668 ID - 32130668 N1 - György Nagy and Nadia M T Roodenrijs = Contributed equally AB - Objective To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). Methods An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. Results Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). Conclusions These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research. LA - English DB - MTMT ER - TY - JOUR AU - Hamar, Attila AU - Hascsi, Zsolt AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Végh, Edit AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Soós, Boglárka AU - Kerekes, György AU - Szekanecz, Éva AU - Hódosi, Katalin AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Seres, Tamás AU - Szekanecz, Zoltán AU - Szamosi, Szilvia TI - Prospective, simultaneous assessment of joint and vascular inflammation by PET/CT in tofacitinib-treated patients with rheumatoid arthritis: associations with vascular and bone status JF - RMD OPEN J2 - RMD OPEN VL - 7 PY - 2021 IS - 3 SP - 1 EP - 10 PG - 10 SN - 2056-5933 DO - 10.1136/rmdopen-2021-001804 UR - https://m2.mtmt.hu/api/publication/32575467 ID - 32575467 N1 - 325871 LA - English DB - MTMT ER - TY - JOUR AU - Hamar, Attila AU - Hascsi, Z. AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Vegh, E. AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Soos, B. AU - Kerekes, György AU - Szekanecz, Éva AU - Hodosi, K. AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Seres, T. AU - Szekanecz, Zoltán AU - Szamosi, Szilvia TI - SIMULTANEOUS ASSESSMENT OF JOINT AND VASCULAR INFLAMMATION BY PET-CT IN TOFACITINIB-TREATED PATIENTS WITH RHEUMATOID ARTHRITIS: A PROSPECTIVE STUDY JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 80 PY - 2021 SP - 425 EP - 425 PG - 1 SN - 0003-4967 DO - 10.1136/annrheumdis-2021-eular.2473 UR - https://m2.mtmt.hu/api/publication/32501310 ID - 32501310 N1 - 334210 LA - English DB - MTMT ER - TY - JOUR AU - Soos, B. AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Vegh, E. AU - Szamosi, Szilvia AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Kerekes, György AU - Szekanecz, Éva AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Christians, U. AU - Klawitter, J. AU - Seres, T. AU - Szekanecz, Zoltán TI - EFFECTS OF TOFACITINIB THERAPY ON ARGININE AND METHIONINE METABOLITES IN ASSOCIATION WITH VASCULAR PATHOPHYSIOLOGY IN RHEUMATOID ARTHRITIS: A METABOLOMIC APPROACH JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 80 PY - 2021 SP - 421 EP - 422 PG - 2 SN - 0003-4967 DO - 10.1136/annrheumdis-2021-eular.1697 UR - https://m2.mtmt.hu/api/publication/32500463 ID - 32500463 N1 - 334209 LA - English DB - MTMT ER -