TY - JOUR
T1 - Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy
T2 - a prospective pilot study
AU - Dijkshoorn, Bas
AU - Hansildaar, Romy
AU - Vedder, Daisy
AU - Soutari, Nida
AU - Rudin, Anna
AU - Nordström, Dan
AU - Gudbjornsson, Bjorn
AU - Lend, Kristina
AU - Uhlig, Till
AU - Haavardsholm, Espen A
AU - Grondal, Gerdur
AU - Hetland, Merete Lund
AU - Heiberg, Marte Schrumpf
AU - Østergaard, Mikkel
AU - Hørslev-Petersen, Kim
AU - Lampa, Jon
AU - van Vollenhoven, Ronald F
AU - Antovic, Aleksandra
AU - Nurmohamed, Michael T
N1 - © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2024/12/31
Y1 - 2024/12/31
N2 - 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.
AB - 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.
KW - Humans
KW - Arthritis, Rheumatoid/drug therapy
KW - Female
KW - Male
KW - Middle Aged
KW - Pilot Projects
KW - Antirheumatic Agents/therapeutic use
KW - Blood Coagulation/drug effects
KW - Prospective Studies
KW - Biomarkers/blood
KW - Adult
KW - Antibodies, Monoclonal, Humanized/therapeutic use
KW - Aged
KW - Treatment Outcome
KW - Hemostasis/drug effects
KW - Methotrexate/therapeutic use
KW - Blood Coagulation Tests
UR - http://www.scopus.com/inward/record.url?scp=85214320687&partnerID=8YFLogxK
U2 - 10.1136/rmdopen-2024-004838
DO - 10.1136/rmdopen-2024-004838
M3 - Journal article
C2 - 39740931
SN - 2056-5933
VL - 10
JO - RMD Open
JF - RMD Open
IS - 4
M1 - e004838
ER -