MACE, VTE Risk Not Increased by Advanced Therapies for Inflammatory Bowel Disease

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Advanced therapies for inflammatory bowel disease, namely small molecules and biologic therapies, did not increase the risk of a major adverse cardiovascular event or venous thromboembolism.

Patients with inflammatory bowel disease (IBD) who received treatment with a biologic therapy appeared to have a lower risk for a major adverse cardiovascular event (MACE) and venous thromboembolism (VTE), according to a retrospective propensity matched TriNeTx database analysis presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, Canada.

The study also looked at small molecule therapies and found similar levels of MACE and VTE with these therapies compared with a propensity matched comparator arm. Findings from the retrospective study are consistent with long-term extension results seen in clinical trials for patients with IBD, according to senior investigator Miguel Regueiro, MD, who presented the results on behalf of his fellow Thabet Qapaja, MD, who could not attend the meeting.

"For those who treat and practice in IBD, these data continue to support and affirm, and hopefully comfort us that we did not see higher rates of VTE and MACE," said Regueiro, chief of Cleveland Clinic's Digestive Disease Institute. "The main question that needs to be asked is will the FDA change in any way the current indication that requires a TNF before upadacitinib [Rinvoq] or tofacitinib [Xeljanz], and that remains to be seen."

The study included patients from the TriNeTx multi-institutional database using ICD-10 codes to identify patients with IBD along with the occurrence of MACE and VTE. Once identified a 1:1 propensity score matching was completed to create a comparator arm using age, race, sex, cardiovascular risk factors, and non-advanced therapy medication use, including immunomodulators, 5-ASAs, and steroids. Events were examined 30 days after initiation of therapy for the occurrence of a cardiovascular event.

The study looked specifically at patients with IBC who received infliximab (Remicade), adalimumab (Humira), golimumab (Simponi), certolizumab (Cimzia), vedolizumab (Entyvio), natalizumab (Tyruko), or ustekinumab (Stelara). The small molecule inhibitors analyzed in the study included tofacitinib, upadacitinib, or ozanimod (Zeposia). Each group was compared with a matched group who did not receive a biologic or small molecule inhibitor. There were 67,607 patients identified who received a biologic and 3194 received a small molecule.

For patients receiving a biologic therapy, coronary artery disease occurred in 4.74% as compared with 6.71% for those in the comparator group (adjust odds ratio [aOR], 0.691; 95% CI, 0.66-0.742; P <.0001). Myocardial infarction occurred in 1.33% of patients receiving a biologic compared with 1.98% for those not receiving these interventions (aOR, 0.662; 95% CI, 0.608-0.721; P <.0001). A stroke was experienced by 1.46% of patients receiving a biologic compared with 2.04% (aOR, 0.71; 95% CI, 0.653-0.771; P <.0001). Venous thromboembolism (either a deep vein thrombosis [DTV] or a pulmonary embolism [PE]) occurred in 4.44% of patients receiving a biologic compared with an incidence of 5.2% in those not receiving biologics (aOR, 0.848; 95% CI, 0.806-0.891; P <.0001).

"Some of this may be driven by the fact that we're decreasing inflammation, which may decrease VTE and MACE, but this study was not prepared to make that evaluation," said Regueiro.

In the small molecule group, a significant difference was not observed between the treatment group and the comparator for MACE or VTE, suggesting no increased risk for an event. For coronary artery disease, 4.5% of patients had an event compared with 4.32% in the comparator group (aOR, 1.046; 95% CI, 0.823-1.328; P = .7148). For myocardial infarction the rates were 0.84% vs 0.81%, with the small molecule and without, respectively (aOR, 1.039; 95% CI, 0.605-1.784; P = .8903). Stroke was experienced by 1.25% in the small molecule group compared with 1.44% for the comparator (aOR, 0.868; 95% CI, 0.567-1.33; P = .5148). VTE was seen in 3.82% of patients in the small molecule group compared with 3.57% for the comparator arm (aOR, 1.073; 95% CI, 0.827-1.392; P = .5957).

"The strength of this study is the large sample size, from healthcare organizations across the United States. Propensity score matching was used to control for variables that may impact MACE and VTE," said Regueiro. "This was a retrospective design, and it was a claim database, which means it does not provide granular detail on such things as disease severity, phenotype, behavior, and others."


Qapaja T, Alchirazi KA, Naser A, et al. Biologic and Small Molecule Therapies Are Not Associated with Increased Major Adverse Cardiovascular Events (MACE) in IBD: A Propensity Matched Cohort Study. Presented at: ACG 2023 Annual Meeting; October 20-25, 2023. Abstract 9.