Cardiovascular Risk in Patients With Inflammatory Bowel Disease on Janus Kinase Inhibitors Versus Tumor Necrosis Factor Inhibitors: A Real-World Study in a Cardiovascular Risk-Enriched Population

Background:
The emergence of janus kinase inhibitors (JAKi) such as tofacitinib and upadacitinib has transformed the management of inflammatory bowel disease (IBD). However, there are growing concerns regarding their cardiovascular safety, since results from the ORAL Surveillance study noted potential risks related to major adverse cardiovascular events (MACE). Although recent studies in patients with IBD have not shown an increased risk of MACE compared to tumor necrosis factor inhibitors (TNFi), there is limited data for patients with cardiovascular risk factors.. The primary aim of this study is to compare the risk of MACE in patients with IBD treated with JAKi compared to those treated with TNFi.
Methods:
This retrospective cohort study utilized the US Collaborative Network within the TriNetX database. We included patients with UC or CD who were >= 50 years old with at least 1 cardiovascular risk factor who were on either a JAKi (tofacitinib or upadacitinib) or TNFi (infliximab or adalimumab). The primary outcome was the incidence of MACE which included acute myocardial infarction (MI), acute heart failure (HF) or stroke within 1 year. Secondary outcomes included all-cause mortality, venous thromboembolism (VTE) and malignancy. One-to-one propensity score matching was performed for demographics, comorbid conditions and IBD medications including steroid use between the cohorts. Subgroup analysis was performed based on the type of JAKi and age (50-64 vs >=65). Risk estimates were expressed as adjusted odds ratio (aOR) with 95% confidence intervals (CI).
Results:
There were 1,050 patients in the JAKi cohort (mean age 61.5 ± 8, White race 77.2%, male 41.5%, Crohn’s disease 41.3%, Upadacitinib 37.2%) and 9,124 patients in the TNFi cohort (mean age 61.2 ± 8, White race 76.7%, male 43.9%, Crohn’s disease 39.1%). The incidence of MACE was 3.10% in the JAKi group compared to 4.27% in the TNFi group with no difference in the risk (aOR 0.70, 95% CI: 0.43-1.16, p=0.17). Additionally, there was no difference in the risk of acute MI (aOR 0.92, 95% CI: 0.41-2.03, p=0.84), acute HF (aOR 0.76, 95% CI: 0.33-1.75, p=0.52) and CVA (aOR 0.6, 95% CI: 0.28-1.29, p=0.19). There was also no significant differences in the risk of malignancy (aOR 0.6, 95% CI: 0.30-1.17, p=0.13), VTE (aOR 0.82, 95% CI 0.41-1.65, p=0.59) and all-cause mortality (aOR 0.66, 95% CI: 0.29-1.48, p=0.31). Furthermore, there was no significant difference in the risk of MACE in patients on tofacitinib and upadacitinib compared to patients in the TNFi cohort. Similarly, there was no difference in the risk of MACE among patients aged 65 years and older between the JAKi and TNFi cohorts.
Conclusions:
Our study found no significant difference in the risk of MACE between patients with IBD treated with JAKi compared with those on TNFi. Despite concerns about increased MACE risk with tofacitinib, our analysis did not reveal a higher cardiovascular risk for JAKi compared to TNFi in a cardiovascular risk-enriched population. These findings suggest that JAKi and TNFi have comparable cardiovascular safety profile, though continued monitoring in high-risk populations and prospective long-term studies are warranted to fully assess cardiovascular safety.