DAY 2 - Risk for Adverse Cardiovascular Events Is Similar with Janus Kinase Inhibitors and Biologic Therapies for Inflammatory Bowel Disease

An analysis presented at the ACG 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania showed that Janus kinase (JAK) inhibitors do not increase the risk for major adverse cardiovascular events (MACE) compared with biologic therapies in people with inflammatory bowel disease (IBD).

Individuals with IBD are vulnerable to MACE and thromboembolic events, including deep vein thrombosis and pulmonary embolism (Biondi RB et al. Clin Exp Gastroenterol 2020; 24:107-13). Although the link between IBD and cardiovascular events remains unclear, the chronic inflammation associated with immune-mediated inflammatory disorders may contribute to the increased risk for MACE, along with traditional cardiovascular risk factors.

While advanced therapies such as JAK inhibitors have changed the therapeutic landscape of IBD, they have also introduced concerns about treatment-associated cardiotoxicity. A meta-analysis of randomized controlled trials published earlier this year showed an increased risk of MACE with both JAK inhibitors and tumor necrosis factor (TNF) blockers compared with placebo (Mattay S et al. Clin Gastroenterol Hepatol 2024; 22:961-970.e12).

In a study conducted at the University of Missouri-Kansas City, internal medicine resident Saqr Alsakarneh, MD and colleagues compared the risk of MACE and venous thromboembolism (VTE) between individuals with IBD who were treated with JAK inhibitors and those who received anti-TNF therapies. The authors used the TriNetX database, which contains the electronic health records of 115 million patients across the United States, to collect information on patients with IBD who were at least 18 years of age and who had started JAK inhibitors or anti-TNF therapies only after being diagnosed with IBD. The search identified 3,740 patients treated with JAK inhibitors who were then matched 1:1 with an equal number of patients treated with anti-TNF agents. None of the participants had a history of MACE or VTE. The propensity-matched cohort analysis showed that 57 (1.76%) of the patients treated with JAK inhibitors and 63 (1.94%) of those treated with anti-TNF therapies experienced MACE.

“There was no difference between the two cohorts in the development of MACE or VTE,” Alsakarneh said during a plenary session. Moreover, subgroup analyses did not reveal any statistically significant differences in the incidence of MACE or VTE when comparing subtypes of IBD, upadacitinib to tofacitinib, or JAK inhibitors to infliximab. Patients aged 65 years or older also had similar rates of cardiovascular and thromboembolic events, regardless of therapy type.

“Our results suggest that patients with IBD, including older patients, who are treated with JAK inhibitors were not at increased risk of MACE or VTE over a 12-month period as compared to those treated with anti-TNF therapy,” Alsakarneh concluded. While these findings may be reassuring to clinicians who must weigh the risk for MACE and other serious adverse events against the benefit of prescribing JAK inhibitors, the author noted that researchers must continue to investigate the safety profile of advanced therapies for IBD in larger cohorts. Many questions are yet to be answered, including those related to the effects of disease severity on cardiovascular risk, dose-dependent risks for MACE or VTE, and long-term cardiovascular outcomes in this population of patients.