Strong association between high disease activity in rheumatoid arthritis and venous thromboembolism

31 Aug 2020

Over time, it has become clear that rheumatoid arthritis (RA) patients are at increased risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE).1 EULAR President Professor Iain McInnes from The University of Glasgow, United Kingdom, shared, "In the case of autoimmune diseases such as RA, the immune system turns against the body and causes inflammation in several places. Inflammation may have a disruptive effect on coagulation."

Furthermore, a nationwide study illustrated that patients with RA have a 3.36-fold and 2.07-fold increased risks of developing DVT and PE than those without RA.1 Interestingly, data from the German register RABBIT revealed that RA patients treated with biological disease-modifying antirheumatic drugs have a significantly reduced risk of serious VTE events.2

Viktor Molander, a Ph.D. student from the Karolinska Institutet in Stockholm, Sweden, noted, "There is a need to better understand how VTE risk areas spread across segments of RA patients, especially with disease activity." According to Molander's data at the EULAR 2020 e-congress, 1 in 100 RA patients, with high disease activity, will develop VTE within one year. These findings revealed a greater than 2-fold VTE risk for patients with RA as opposed to patients in remission.3

The nationwide register-based cohort study in Sweden was conducted to investigate the relationship between clinical RA disease activity and the incidence of VTE. RA patients enrolled in the study were identified from the Swedish Rheumatology Quality Register (SRQ) from 2006 to 2017. A visit followed by a VTE event was categorized as a case, all other visits were used as controls. The Disease Activity Score 28 (DAS28) assesses the disease activity of RA based on the assessment of 28 defined joints and was used to stratify the RA patients into four groups: Remission (0-2.5), low (2.6-3.1), moderate (3.2-5.1), or high (>5.1).3

Subsequently, for a duration of 1 year, 46,311 RA patients were assessed from data obtained through a total of 320,094 visits. The median age was 63 years, and the median RA duration was 8.7 years. Applying a logistic regression model with robust cluster standard error, Molander revealed that among 2,257 visits (0.7% of all visits), 1,345 unique individuals were followed by a VTE event within the one-year window, of which 1,391 were DVT cases and 866 were PE events. Interestingly, although 74% of the patients were female, VTE incidences were slightly higher in males. As per past data, the occurrence of VTE increased with age.3

Using DAS28 for stratification, the estimated 1-year risk of a VTE incidence was increased to 1.1% for patients with DAS28 >5.1 when compared to 0.5% in patients in DAS28 remission.3 The age- and sex-adjusted odds ratio for a VTE event in highly active RA versus disease in remission was 2.12 (95% CI: 1.80-2.47).3

Notably, risk ratios assessing the association between the DAS28 categories and VTE established a clear link between VTE risk with disease activity and higher score in health assessment questionnaire (HAQ). Primarily, the observed absolute 1-year risk for VTE was distributed within all the categories and not influenced by any key factor.3

Interestingly, analysis for estimated risk ratio stratified by VTE subtypes demonstrated a 3-fold higher risk of PE in patients with high disease activity when compared to patients in remission. Also, PE events were twice higher than DVT events (Figure 1). Summarizing the study data, Viktor Molander shared, "We found a strong association between clinical RA disease activity measured through DAS28 and risk of VTE.”

The study proved the feasibility of employing RA disease activity as a tool for VTE risk stratification. Furthermore, given the growing evidence of higher VTE risk in RA patients undergoing janus kinase (JAK) inhibitor therapy4 this data highlighted the importance of taking the pre-existing VTE risks, which are already present in RA patients, into account before the administration of any new treatment regimen.

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