Early Control of Rheumatoid Arthritis Improves Hemostatic Imbalance

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Effective antirheumatic treatments, especially tocilizumab and other biological drugs, improved hemostatic imbalances in patients with newly diagnosed rheumatoid arthritis (RA) during the first 24 weeks after diagnosis, possibly mitigating elevated thrombosis risks in this population.¹

These findings, from a study published in RMD Open, were led by Bas Dijkshoorn, MD, MSc, PhD candidate, a visiting fellow of Rheumatology at Amsterdam Rheumatology and Immunology Center in the Netherlands.

“RA is associated with an increased cardiovascular burden, such as atherosclerosis and venous thromboembolism (VTE) with an almost 2-fold higher risk compared with the healthy population. It was recently shown that the relative risk for VTE is higher in RA patients with high disease activity, compared with patients in remission. Additionally, the increased risk for VTE shown in the ORAL surveillance trial highlights the continued importance of evaluating VTE risk when initiating new treatments. The increased incidence of VTE in patients with RA points towards the presence of a procoagulant state in these patients,” Dijkshoorn and colleagues wrote.¹

The study enrolled 24 participants with newly diagnosed RA to start methotrexate and a randomized additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. The investigators analyzed several biomarkers for hemostasis including overall hemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single hemostatic factors such as fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) at baseline, 12 and 24 weeks after the start of the treatment.

Dijkshoorn and colleagues found that patients had elevated levels of fibrinogen, F1+2, D-dimer, ETP and OHP at baseline compared with reference values. After 24 weeks, all patients had significant reductions in F1+2 (P <.01), fibrinogen (P <.01), D-dimer (P <.01), OHP (P <.01), ETP (P <.01), CLT (P <.01), TAFI (P <.01) and an increase of overall fibrinolytic potential (P <.01). Notably, tocilizumab treatment yielded the most significant reduction of OHP (73%; P <.01) compared with certolizumab pegol (32%; P <.01), abatacept (24%; P = .25) or conventional treatment (7%; P = .66).¹

“We demonstrated that patients with untreated early RA have significantly impaired coagulation and fibrinolysis before treatment. To the best of our knowledge, this is the first study which examines different treatment strategies on this hemostatic imbalance. We were able to demonstrate that treatment of early RA reduced the pro-coagulant state present in newly diagnosed patients, with biological treatments being the most effective, in particular IL-6 receptor inhibition. This difference was most profound in the reduction of fibrinogen as in the tocilizumab group there was a reduction of 63% compared with 8% in the conventional treatment group,” Dijkshoorn and colleagues concluded.¹

Other recent research from November’s American College of Rheumatology (ACR) Convergence 2024 evaluating cardiovascular outcomes in people with RA found that glucocorticosteroids (GCs) increased cardiovascular disease (CVD) and infection mortality risk even after cessation.²

Investigators found that the risk of mortality due to CVD or infection increased by 7.5% and 6.8%, respectively, for every year of GC use and decreased by 1.3% and 4.9%, respectively, for every year after stopping GC. People who used GC for over 2 years and 3 years had elevated risks of CVD and infection-related mortality, respectively, that never returned to pre-GC use levels. In people who used GC for 6, 12, and 24 months, it took 1.5, 3.5 and 10 years after cessation for risk of CVD mortality to decrease to that of someone prior to starting GC. Similarly, it took 2.5, 3.5, and 5.5 years, respectively, after cessation for risk of deaths from infection to decrease accordingly.²

“They have risks and benefits, and those risks and benefits aren’t the same for every disease or every person. It’s important to have clear, ongoing conversations about steroids and to recognize that these risks include withdrawal symptoms when long-term steroids are tapered,” Beth Wallace, MD, assistant professor. University of Michigan and VA Ann Arbor Healthcare Center, said in a related statement.³

REFERENCES

1. Dijkshoorn B, Hansildaar R, Vedder D, et al. Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study. RMD Open 2024;10:e004838. doi: 10.1136/rmdopen-2024-004838

2. Lacaille D, Danieli C, Moolooghy K, Abrahamowicz M. Changes in Mortality Risk After Stopping Glucocorticosteroids – a Population-based Study in Rheumatoid Arthritis. Presented at: ACR Convergence 2024; November 15-19; Washington, DC. Abstract 2673.

3. Corticosteroids: One Size Does Not Fit All. News release. ACR. November 14, 2024.