Major Adverse Cardiovascular Events and VTE in Patients with IBD Taking Anti-TNF versus JAK Inhibitors: A Multicenter...

Inflammatory bowel disease (IBD) is associated with an increased risk of major adverse cardiovascular events (MACE). Janus kinase inhibitors (JAKi) are approved to treat IBD, but there are concerns over whether they increase the risk of MACE or venous thromboembolism (VTE) in patients with IBD. We aimed to compare the incidence risk of MACE and VTE in patients with IBD treated with JAKi agents versus anti-TNFs.

We conducted a retrospective cohort study using the TriNetX database to identify patients  ≥ 18 years with IBD and treated with JAKi or anti-TNF therapy. Patients in the JAKi cohort were matched with patients treated with anti-TNF by using 1:1 propensity score matching. Patients with a history of a prior cardiovascular event were excluded from the analysis. Co-primary outcomes were MACE and VTE within 1-year after medication initiation. Additional subgroup analyses were performed based on age, sex, and IBD type. Kaplan-Meier analysis with adjusted hazard ratios (HRs) and 95% CIs were used to compare time-to-event rates.

In total, there were 8942 patients in the JAKi cohort matched with 8942 patients in the anti-TNF cohort. There was no difference between the two cohorts in the development of MACE (aHR: 1.08; 95% CI: 0.87-1.33; p = 0.49) or VTE (aHR: 1.06; 95% CI: 0.84-1.36; p = 0.61). In patients aged ≥ 65 years, there was no statistically significant difference between the two cohorts in MACE outcomes (aHR: 0.95; 95% CI: 0.69-1.31; p = 0.75). Consistent findings were observed when comparing ulcerative colitis to Crohn's disease, upadacitinib to tofacitinib, or JAKi to infliximab.

Our results suggest that patients with IBD, including patients ≥ 65 years, who are treated with JAKi, were not at increased risk of MACE or VTE over a 12-month period as compared to those treated with anti-TNF therapy. Further prospective studies are warranted to confirm these findings.