Dijkshoorn Bas, Hansildaar Romy, Vedder Daisy, Soutari Nida, Rudin Anna, Nordström Dan, Gudbjornsson Bjorn, Lend Kristina, Uhlig Till, Haavardsholm Espen A, Grondal Gerdur, Hetland Merete Lund, Heiberg Marte Schrumpf, Østergaard Mikkel, Hørslev-Petersen Kim, Lampa Jon, van Vollenhoven Ronald F, Antovic Aleksandra, Nurmohamed Michael T
Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands.
Department of Molecular Medicine and Surgery Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
RMD Open. 2024 Dec 31;10(4):e004838. doi: 10.1136/rmdopen-2024-004838.
To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).
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.
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).
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.
评估治疗对早期类风湿关节炎（RA）患者止血参数的影响。
新诊断的RA患者开始使用甲氨蝶呤，并随机分为接受额外的传统治疗、赛妥珠单抗聚乙二醇化、阿巴西普或托珠单抗治疗。分析了几种止血生物标志物，包括两种整体止血检测的参数——整体止血潜力（OHP）和内源性凝血酶潜力（ETP），以及单一止血因子——纤维蛋白原、凝血酶原片段1+2（F1+2）、D-二聚体、凝血酶激活的纤维蛋白溶解抑制剂（TAFI）和凝血块溶解时间（CLT），在24例患者的基线、治疗开始后12周和24周时进行检测。
在基线时，与参考值相比，患者的以下生物标志物水平升高：纤维蛋白原、F1+2、D-二聚体以及两种整体止血检测的参数，即ETP和OHP。24周后，我们观察到F1+2（p<0.01）、纤维蛋白原（p<0.01）、D-二聚体（p<0.01）、OHP（p<0.01）、ETP（p<0.01）、CLT（p<0.01）、TAFI（p<0.01）显著降低，OFP升高（p<0.01）。24周后，托珠单抗治疗导致整体止血检测的降低最为显著，即OHP降低73%（p<0.01），而赛妥珠单抗聚乙二醇化组为32%（p<0.01），阿巴西普组为24%（p=0.25），传统治疗组为7%（p=0.66）。
我们的结果表明，新诊断的RA患者存在凝血激活增强和纤维蛋白溶解受损的情况。诊断后的前24周内有效的抗风湿治疗改善了这种止血失衡，与传统治疗相比，生物药物尤其是托珠单抗具有显著效果。
