Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study

Objectives To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).Methods Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomar...

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Main Authors: Ronald F van Vollenhoven, Merete Lund Hetland, Till Uhlig, Espen A Haavardsholm, Dan Nordström, Aleksandra Antovic, Mikkel Østergaard, Michael T Nurmohamed, Bjorn Gudbjornsson, Gerður Gröndal, Kim Hørslev-Petersen, Anna Rudin, Jon Lampa, Kristina Lend, Daisy Vedder, Marte Schrumpf Heiberg, Bas Dijkshoorn, Romy Hansildaar, Nida Soutari
Format: Article
Language:English
Published: BMJ Publishing Group 2024-12-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/10/4/e004838.full
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author Ronald F van Vollenhoven
Merete Lund Hetland
Till Uhlig
Espen A Haavardsholm
Dan Nordström
Aleksandra Antovic
Mikkel Østergaard
Michael T Nurmohamed
Bjorn Gudbjornsson
Gerður Gröndal
Kim Hørslev-Petersen
Anna Rudin
Jon Lampa
Kristina Lend
Daisy Vedder
Marte Schrumpf Heiberg
Bas Dijkshoorn
Romy Hansildaar
Nida Soutari
author_facet Ronald F van Vollenhoven
Merete Lund Hetland
Till Uhlig
Espen A Haavardsholm
Dan Nordström
Aleksandra Antovic
Mikkel Østergaard
Michael T Nurmohamed
Bjorn Gudbjornsson
Gerður Gröndal
Kim Hørslev-Petersen
Anna Rudin
Jon Lampa
Kristina Lend
Daisy Vedder
Marte Schrumpf Heiberg
Bas Dijkshoorn
Romy Hansildaar
Nida Soutari
author_sort Ronald F van Vollenhoven
collection DOAJ
description Objectives To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).Methods Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays—overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors—fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment.Results At baseline, patients had elevated levels of the following biomarkers compared with reference values: fibrinogen, F1+2, D-dimer and parameters of the two global haemostatic assays, that is, ETP and OHP. After 24 weeks we observed a significant reduction in F1+2 (p<0.01), fibrinogen (p<0.01), D-dimer (p<0.01), OHP (p<0.01), ETP (p<0.01), CLT (p<0.01), TAFI (p<0.01) and an increase of OFP (p<0.01). Tocilizumab treatment resulted in the most significant reduction of global haemostatic assays after 24 weeks, that is, a reduction of OHP 73% (p<0.01) compared with certolizumab pegol arm 32% (p<0.01), abatacept arm 24% (p=0.25) or conventional treatment arm 7% (p=0.66).Conclusion Newly diagnosed RA patients have enhanced coagulation activation and impaired fibrinolysis as demonstrated by our results. Effective antirheumatic treatments during the first 24 weeks after diagnosis improved this haemostatic imbalance, with prominent effects of biological drugs and especially tocilizumab, compared with conventional treatment.
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spelling doaj-art-81133f41e63b4acdbcd5370d2a39568b2025-08-20T02:40:02ZengBMJ Publishing GroupRMD Open2056-59332024-12-0110410.1136/rmdopen-2024-004838Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot studyRonald F van Vollenhoven0Merete Lund Hetland1Till Uhlig2Espen A Haavardsholm3Dan Nordström4Aleksandra Antovic5Mikkel Østergaard6Michael T Nurmohamed7Bjorn Gudbjornsson8Gerður Gröndal9Kim Hørslev-Petersen10Anna Rudin11Jon Lampa12Kristina Lend13Daisy Vedder14Marte Schrumpf Heiberg15Bas Dijkshoorn16Romy Hansildaar17Nida Soutari18Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The NetherlandsDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkRheumatology, Diakonhjemmet Hospital, Oslo, NorwayRheumatology, Diakonhjemmet Hospital, Oslo, NorwayDepartment of Medicine, Helsinki University Central Hospital, Helsinki, FinlandDepartment of Medicine Solna, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkRheumatology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Rheumatology, Centre for Rheumatology Research, Reykjavik, IcelandLandspitali University Hospital, Reykjavk, IcelandDepartment of Rheumatology, Danish Hospital for Rheumatic Diseases, Sønderborg, DenmarkDepartment of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenRheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, SwedenDepartment of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam Rheumatology Center, Amsterdam, The NetherlandsRheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The NetherlandsRheumatology, Diakonhjemmet Hospital, Oslo, NorwayRheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The NetherlandsRheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The NetherlandsDepartment of Molecular Medicine and Surgery Clinical Chemistry, Karolinska University Hospital, Stockholm, SwedenObjectives To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).Methods Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays—overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors—fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment.Results At baseline, patients had elevated levels of the following biomarkers compared with reference values: fibrinogen, F1+2, D-dimer and parameters of the two global haemostatic assays, that is, ETP and OHP. After 24 weeks we observed a significant reduction in F1+2 (p<0.01), fibrinogen (p<0.01), D-dimer (p<0.01), OHP (p<0.01), ETP (p<0.01), CLT (p<0.01), TAFI (p<0.01) and an increase of OFP (p<0.01). Tocilizumab treatment resulted in the most significant reduction of global haemostatic assays after 24 weeks, that is, a reduction of OHP 73% (p<0.01) compared with certolizumab pegol arm 32% (p<0.01), abatacept arm 24% (p=0.25) or conventional treatment arm 7% (p=0.66).Conclusion Newly diagnosed RA patients have enhanced coagulation activation and impaired fibrinolysis as demonstrated by our results. Effective antirheumatic treatments during the first 24 weeks after diagnosis improved this haemostatic imbalance, with prominent effects of biological drugs and especially tocilizumab, compared with conventional treatment.https://rmdopen.bmj.com/content/10/4/e004838.full
spellingShingle Ronald F van Vollenhoven
Merete Lund Hetland
Till Uhlig
Espen A Haavardsholm
Dan Nordström
Aleksandra Antovic
Mikkel Østergaard
Michael T Nurmohamed
Bjorn Gudbjornsson
Gerður Gröndal
Kim Hørslev-Petersen
Anna Rudin
Jon Lampa
Kristina Lend
Daisy Vedder
Marte Schrumpf Heiberg
Bas Dijkshoorn
Romy Hansildaar
Nida Soutari
Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study
RMD Open
title Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study
title_full Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study
title_fullStr Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study
title_full_unstemmed Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study
title_short Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study
title_sort impaired coagulation parameters in early ra are restored by effective antirheumatic therapy a prospective pilot study
url https://rmdopen.bmj.com/content/10/4/e004838.full
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