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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BMJ Publishing Group
2024-12-01
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| 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. |
| format | Article |
| id | doaj-art-81133f41e63b4acdbcd5370d2a39568b |
| institution | DOAJ |
| issn | 2056-5933 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
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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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