No Increased Risk of Cardiovascular Events in IBD Patients Taking JAK Inhibitors

It is known that people living with inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, are twice as likely to experience major adverse cardiovascular events (MACE) compared with the general population. Definitions for MACE can vary from one source to another. However, they typically include nonfatal myocardial infarction, nonfatal stroke, and cardiovascular mortality.

Janus kinase (JAK) inhibitors are oral small molecules used to treat various chronic inflammatory conditions, including ulcerative colitis, Crohn’s disease, and rheumatoid arthritis. At least 10 JAK inhibitors are approved for use in the United States. Xeljanz (tofacitinib) and Rinvoq (upadacitinib) are approved to treat ulcerative colitis, Crohn’s disease, and rheumatoid arthritis, among other conditions.

Concerns about the increased risk of MACE and pulmonary embolism in patients with rheumatoid arthritis observed in a Xeljanz clinical trial led to the addition of a boxed warning by the FDA for any JAK inhibitor approved to treat rheumatoid arthritis. Xeljanz and Rinvoq both carry boxed warnings for the increased risk of MACE and thrombosis in patients with rheumatoid arthritis. But is is unclear whether this risk carries over to patients with IBD.

In an abstract presented t the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in October, Saqr Alsakarneh, M.D., from the University of Missouri – Kansas City School of Medicine, and his colleagues compared the risk of MACE and venous thromboembolism (VTE) in patients with IBD taking JAK inhibitors versus tumor necrosis factor (TNF) blockers. The primary outcomes were the occurrence of MACE or VTE within one year

The researchers used data from the TriNetX database to identify adults with IBD receiving treatment with a TNF inhibitor or a JAK inhibitor. A total of 3,740 patients taking JAK inhibitors were propensity-matched with 3,740 patients taking TNF blockers. The study excluded patients with a prior history of cardiovascular events.

Alsakarneh and his team found no significant difference in the development of MACE between patients taking JAK inhibitors compard with TNF inhibitors (1.76% versus 1.94%, respectively). No difference was found between the two groups when comparing VTE events.

After subgroup analysis, no differences were found between patients with ulcerative colitis versus Crohn’s disease. Results were also similar when comparing Xeljanz to Rinvoq or JAK inhibitors to the TNF blocker infliximab.

The only difference observed was with intestinal resection surgery. Patients taking JAK inhibitors were more likely to undergo this procedure compared with those in the TNF inhibitor group, although no difference in corticosteroid use was found between the two groups.

The researchers concluded that their findings suggest that JAK inhibitors do not increase the risk for MACE or VTE in patients with ulcerative colitis or Crohn’s disease. They recommend further prospective research to confirm these results.