JAK inhibitors & MACE

October 15, 2024

Issue 20

Clinical Question

What is the risk of major adverse cardiovascular events with JAK inhibitors?

Editor’s Bottom Line

These reassuring data do not show an increased risk of major adverse cardiovascular events specific to JAK inhibitors among patients treated for immune mediated inflammatory disorders including IBD.

Reference

Mattay SS, Zamani M, Saturno D, et al. Risk of Major Adverse Cardiovascular Events in Immune-Mediated Inflammatory Disorders on Biologics and Small Molecules: Network Meta-Analysis. Clin Gastroenterol Hepatol. 2024;22(5):961–70.e12. https://www.cghjournal.org/article

Synopsis

To determine the relative risk of a major adverse cardiovascular event (MACE) in patients receiving Janus kinase (JAK) inhibitors, researchers performed a network meta-analysis of 36 randomized controlled trials and four cohort studies, including 126,961 adults with inflammatory bowel disease, rheumatoid arthritis, psoriasis, psoriatic arthritis or ankylosing spondylitis.

The included studies had documented rates of myocardial infarction, cerebrovascular accident, unstable angina, cardiovascular death, or heart failure—all considered a MACE. Studies included use of JAK inhibitors, anti-interleukin (IL)-23 antibodies, anti-IL-12/23 antibodies, anti-tumor necrosis factor (anti-TNF) agents, or placebo.

In the randomized, controlled trials, data revealed 25 instances of a MACE in the 8,743 patients treated with a JAK inhibitor, compared to six cases of a MACE among the 3,828 placebo recipients. In the anti-TNF randomized, controlled trials, there were 36 instances of a MACE among 8,818 patients receiving active treatment, compared to eight instances among the 4,851 placebo recipients. Finally, 13 and three cases of a MACE occurred among those receiving an anti-IL-12/23 antibody or a placebo, respectively, in randomized trials of that drug class.

Cohort data were only analyzed for psoriasis patients, none of whom received a JAK inhibitor. The data showed 119 cases of MACE among 14,669 anti-IL-12/23 antibody recipients and 46 MACE cases among 60,009 anti-TNF recipients.

Statistical analyses determined that all drug classes were linked with an increased risk of MACE, compared with placebo. The risk was similar for anti-TNF drugs (Odds Ratio [OR]: 2.49; 95% Confidence Interval [CI], 1.14–5.62) and JAK inhibitors (OR: 2.64; 95% CI, 1.26–5.99), and slightly higher for anti-IL-12/23 antibodies (OR: 3.15; 95% CI, 1.01–13.35).

The risk of a MACE did not differ by type of immune-mediated disease.

Details

Study Design: Systematic review and network meta-analysis
Funding: Pfizer, The American College of Gastroenterology, the Crohn’s and Colitis Foundation and the Lawrence C. Pakula MD IBD Education and Innovation Fund.
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 1a