TNF Inhibitors, Thiopurines May Help Reduce Recurrent Acute Arterial Events

TNF Inhibitors, Thiopurines May Help Reduce Recurrent Acute Arterial Events

July 20, 2022 0 By Jennifer Walker

Patients with inflammatory bowel disease (IBD) who experienced an acute arterial event had a lower risk of recurrent events after receiving tumor necrosis factor (TNF) inhibitors or thiopurines, a French population-based cohort study found.

Among over 27,000 patients, the risk of recurrent acute arterial events — including ischemic heart disease, cerebrovascular disease, and peripheral artery disease — were lower among those who used TNF inhibitors (HR 0.75, 95% CI 0.63-0.90) or thiopurines (HR 0.76, 95% CI 0.66-0.88), reported Julien Kirchgesner, MD, PhD, of the Saint-Antoine Hospital in Paris, and colleagues.

Exposure to combination therapy appeared also to be linked with a lower risk of recurrent events, but this did not reach significance, they noted in Clinical Gastroenterology and Hepatology.

“This study provides new data for the benefit-risk assessment of anti-TNF and thiopurines in patients with IBD and a previous history of acute arterial event,” Kirchgesner and team concluded.

In subgroup analyses, the magnitude of risk reduction was similar between men and women taking either treatment, but was stronger for those ages 18 to 54 receiving TNF inhibitors versus those ages 55 and up. Of note, the trend for risk reduction was more prominent for Crohn’s disease patients taking TNF inhibitors and for ulcerative colitis patients taking thiopurines.

IBD patients are at greater risk for acute arterial events, which may be caused by chronic systemic inflammation that progresses to atherosclerosis, Kirchgesner’s group noted, and treatment with TNF inhibitors has been found to be associated with a protective effect against the first occurrence of these events.

“These data are important, as while TNF antagonists have previously been associated with lower incidence of initial arterial events, the risk of subsequent events following a first episode have not been reported, and they inform our ability to treat IBD with effective therapies despite the prior occurrence of cardiovascular events,” said Dana Lukin, MD, PhD, of Weill Cornell Medicine in New York City, who was not involved in the study.

“The demonstration that effective anti-inflammatory, disease-modifying therapies reduce cardiovascular risk factors provides additional strong data that halting the activity of systemic IBD is associated with reduced complications,” Lukin told MedPage Today.

For this study, Kirchgesner and colleagues examined French nationwide health insurance data on 27,185 IBD patients (mean age 66, 62% men) from January 2009 to December 2018. About 37% of patients had Crohn’s disease, and 63.4% had ulcerative colitis. Mean IBD duration was about 6 years.

All patients experienced an acute arterial event prior to Jan. 1, 2018; 66.2% had ischemic heart disease, 26.9% had cerebrovascular disease, and 14.7% had peripheral artery disease.

Of these patients, 82.8% were unexposed to TNF inhibitors or thiopurines, while 9.5% and 11.6% were exposed to TNF inhibitors and thiopurines, respectively. Only 0.5% received combination therapy.

Patients taking adalimumab (Humira), golimumab (Simponi), or thiopurines such as azathioprine or 6-mercaptopurine were considered exposed after 1 month of use, while those on infliximab (Remicade) were considered exposed after 2 months of use.

Over a median follow-up of 4 years, 6,865 recurrent acute arterial events occurred (56.7% with ischemic heart disease, 22.7% with peripheral artery disease, and 20.6% with cerebrovascular disease). After 5 years, the cumulative incidence of recurrent events was 24.8%.

Kirchgesner and team noted that they used disease definitions that were not previously validated, limiting interpretation of the results. Furthermore, the insurance data used in the study lacked complete information on chronic alcohol use, smoking, and obesity, which were potentially underestimated, and data on lifestyle and behavioral factors were not available.

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    Zaina Hamza is a staff writer for MedPage Today, covering Gastroenterology and Infectious disease. She is based in Chicago.

Disclosures

Kirchgesner reported receiving funding from Gilead, Pfizer, and Roche. Co-authors reported receiving funding from AbbVie, Bristol Myers Squibb, Celltrion, Ferring Pharmaceuticals, Hospira-Pfizer, Janssen, MSD, Mylan, Takeda, and Tillotts.