LIVERPOOL, ENGLAND — People with rheumatoid arthritis (RA) have a consistently higher risk for venous thromboembolism (VTE) than the general population, but the reasons for this remain unclear, research presented at the annual meeting of the British Society for Rheumatology (BSR) reaffirmed.
Regardless of age, sex, body mass index (BMI), duration of disease, use of estrogen-based oral contraceptives, or hormone replacement therapy (HRT), people with RA are more likely to experience a pulmonary embolism or deep vein thrombosis than those without RA.
However, “these are rare events,” James Galloway, MBChB, PhD, professor of rheumatology and deputy head of the Centre for Rheumatic Diseases at King’s College London in England, said at the meeting.
In one analysis of data from 117,050 individuals living in England and Wales that are held within a large primary care practice database, Dr. Galloway and colleagues found that the unadjusted incidence of VTE in people diagnosed with RA (n = 23,410) was 0.44% vs 0.26% for matched controls within the general population (n = 93,640).
RA and VTE Risk
The overall risk for VTE was 46% higher among people with RA than among those without, although the absolute difference was small, Dr. Galloway reported.
“RA is associated with an increased risk of VTE; that’s been well described over the years,” Dr. Galloway told this news organization. Past research into why there is an elevated risk for VTE in patients with RA has often focused on the role of disease activity and inflammation.
“In the last few years, a new class of drugs, the JAK [Janus kinase] inhibitors, have emerged in which we have seen a signal of increased VTE risk from a number of studies. And I think that puts a spotlight on our understanding of VTE risk,” Dr. Galloway said.
He added “JAK inhibitors are very powerful at controlling inflammation, but if you take away inflammation, there is still an excess risk. What else could be driving that?”
To examine the excess risk for VTE seen in people with RA, Dr. Galloway and colleagues performed three separate analyses using data collected between January 1999 and December 2018 by the Royal College of General Practitioners Research and Surveillance Center.
One analysis looked at VTE risk according to age, sex, and BMI; another looked at the effect of the duration of RA; and a third analysis focused on the use of estrogen-based oral contraceptives or HRT.
For all three analyses, those with RA were matched in a 4:1 ratio to people from the general population without RA on the basis of current age, sex, calendar time, and years since registration at the primary care practice.
Observational Data Challenged
“These are observational data, so it’s important to weigh up the strengths and limitations,” Dr. Galloway acknowledged. Strengths are the large sample size and long follow-up provided by the database, which assesses and monitors more than 2000 primary care practices in England and Wales.
Confounding is still possible, despite adjusting for multiple factors that included sociodemographic factors; clinical features; and VTE risk factors such as smoking status, alcohol use, thrombophilia, reduced mobility, lower limb fracture, and a family history of VTE if data had been available. There wasn’t information on disease activity, for example, and disease duration was used as a surrogate marker for this.
Sitting in the audience, Marwan Bukhari, MBBS, PhD, challenged the population-matching process.
“Do you think maybe it was the matching that was the problem?” asked Dr. Bukhari, who is consultant rheumatologist at University Hospitals of Morecambe Bay NHS Foundation Trust and an honorary senior lecturer at the University of Manchester, both in England.
“They’re not entirely matched completely, correctly. Even if it is 4:1, there’s a difference between the populations,” he said.