Early TNF Inhibitor Initiation in Ankylosing Spondylitis Linked to Increased Cardiovascular Risk

Results indicate early initiation of tumor necrosis factor (TNF) inhibitors in a veterans population was associated with a 17% increase in incident cardiovascular disease and a 22% increase in major events.

A version of this article was originally published on HCPLive. This version has been lightly edited.

Early initiation of tumor necrosis factor (TNF) inhibitors in ankylosing spondylitis could increase future risk of cardiovascular disease, according to a new study presented at the American College of Rheumatology (ACR) Convergence 2022.

An analysis of more than 17,000 veterans with ankylosing spondylitis, results of the study indicate early initiation of TNF inhibitors in this patient population was associated with a 17% increase in incident cardiovascular disease and a 22% increase in major events.

“We designed the study with the overall hypothesis that the use of TNF inhibitors, which reduce inflammation and thus cardiovascular risk, would be associated with lower risk for our cardiovascular outcomes. That we saw the opposite association, that early use of TNF inhibitors was associated with a higher risk of incident cardiovascular outcomes, was a bit surprising,” said lead investigator Jean Liew, MD, MS, assistant professor of rheumatology at Boston University School of Medicine, in a statement from the ACR.

The study was led by Lieu and colleagues from the VA Boston Healthcare System as well as other Boston-based institutions. The current study sough to explore whether the anti-inflammatory effects of TNF inhibitors may confer some cardioprotective benefit in patients with ankylosing spondylitis. To do so, investigators designed their study as a retrospective cohort analysis leveraging data from the Veterans Affairs Corporate Data Warehouse. Through a search of this database, investigators identified 17,666 patients with ankylosing spondylitis receiving treatment between 2002-2019.

For the purpose of analysis, a diagnosis of ankylosing spondylitis was determined through the presence of 1 or more inpatient or 2 or more outpatient ICD codes for ankylosing spondylitis at least 6 weeks apart. Early TNF inhibitor exposure was assessed during the 12-month period following the index date. The primary outcome of interest was incident cardiovascular disease, which was identified using ICD codes for coronary artery disease, myocardial infarction, or ischemic stroke. Investigators noted myocardial infarction, venous thromboembolism (VTE), stroke, all-cause mortality, and major adverse cardiovascular events (MACE), which included myocardial infarction, stroke, and CV death, served as secondary outcomes of interest for the study.

The 17,666-person cohort had a mean follow-up of 6.0 (4.4) years and a mean age of 59.5 years; most—91.2%—were male, and 79.8% were White. Overall, 15,345 were non-TNF initiators and 232 were classified as TNF initiators. During the follow-up period, 15.1% of TNF initiators experienced incident cardiovascular disease compared to 19.7% of on initiators. Using propensity score matching, investigators’ analysis demonstrated early TNF initiation was associated with an increased risk of incident cardiovascular disease (HR 1.17; 95% CI, 1.01-1.35), stroke (HR, 1.24; 95% CI, 1.03-1.50), and MACE (HR, 1.22; 95% CI, 1.03-1.45) in the overall study cohort. Investigators noted these associations persisted in subgroup analyses linked to 2011-2019.

“The whole healthcare team needs to be cognizant of screening for and treating traditional cardiovascular risk factors like hypertension and hyperlipidemia,” Liew added. “This burden cannot be placed on either the rheumatologist alone, who doesn’t typically manage these conditions, or the primary care provider alone who is likely unaware of the heightened cardiovascular risk.”


Liew J, Treu T, Park Y, et al. The association of early TNF inhibitor use with incident cardiovascular events in ankylosing spondylitis. Presented at: ACR Convergence 2022; Philadelpia, PA. Abstract 0415.

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