Bas Dijkshoorn, Romy Hansildaar, Daisy Vedder, Nida Soutari, Anna Rudin, Dan Nordström, Bjorn Gudbjornsson, Kristina Lend, Till Uhlig, Espen A Haavardsholm, Gerdur Grondal, Merete Lund Hetland, Marte Schrumpf Heiberg, Mikkel Østergaard, Kim Hørslev-Petersen, Jon Lampa, Ronald F van Vollenhoven, Aleksandra Antovic, Michael T Nurmohamed
{"title":"早期RA的凝血参数受损可通过有效的抗风湿病治疗恢复:一项前瞻性的初步研究。","authors":"Bas Dijkshoorn, Romy Hansildaar, Daisy Vedder, Nida Soutari, Anna Rudin, Dan Nordström, Bjorn Gudbjornsson, Kristina Lend, Till Uhlig, Espen A Haavardsholm, Gerdur Grondal, Merete Lund Hetland, Marte Schrumpf Heiberg, Mikkel Østergaard, Kim Hørslev-Petersen, Jon Lampa, Ronald F van Vollenhoven, Aleksandra Antovic, Michael T Nurmohamed","doi":"10.1136/rmdopen-2024-004838","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748942/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study.\",\"authors\":\"Bas Dijkshoorn, Romy Hansildaar, Daisy Vedder, Nida Soutari, Anna Rudin, Dan Nordström, Bjorn Gudbjornsson, Kristina Lend, Till Uhlig, Espen A Haavardsholm, Gerdur Grondal, Merete Lund Hetland, Marte Schrumpf Heiberg, Mikkel Østergaard, Kim Hørslev-Petersen, Jon Lampa, Ronald F van Vollenhoven, Aleksandra Antovic, Michael T Nurmohamed\",\"doi\":\"10.1136/rmdopen-2024-004838\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":21396,\"journal\":{\"name\":\"RMD Open\",\"volume\":\"10 4\",\"pages\":\"\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-12-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748942/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RMD Open\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/rmdopen-2024-004838\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RMD Open","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/rmdopen-2024-004838","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
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 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.
期刊介绍:
RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.