JAK Inhibitors Vs Anti-TNF: No Increased Risk of MACE in IBD

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti-tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis to Crohn’s disease, upadacitinib to tofacitinib, or JAKi to infliximab.
“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri-Kansas City School of Medicine, Kansas City.
Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.
“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.
Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.
Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.
After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).
Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).
In addition, there were no differences when comparing Crohn’s disease to ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib to tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications to infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).
Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).
The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings, he added.
“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week (DDW) that’s being confirmed in this data,” said Miguel Regueiro, MD, chief of Cleveland Clinic’s Digestive Disease Institute. Regueiro, who wasn’t involved with the study, attended the conference session.
“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [US Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”
The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures. 
 
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