Among patients with inflammatory bowel disease (IBD), treatment with Janus kinase inhibitors (JAKi) does not increase the risk of major adverse cardiovascular events (MACE) compared with tumour necrosis factor inhibitors (TNFi), according to a study presented at AIBD 2024.

“The emergence of JAKi such as tofacitinib and upadacitinib has transformed the management of IBD. However, there are growing concerns regarding their cardiovascular (CV) safety, since results from the ORAL Surveillance study noted potential risks related to MACE,” said the researchers.

Hence, the researchers conducted a retrospective cohort study involving patients with IBD, such as ulcerative colitis or Crohn’s disease, who had ≥1 CV risk factor and treated with either JAKi (tofacitinib or upadacitinib; n=1,050, mean age 61.5 years) or TNFi (infliximab or adalimumab; n=9,124, mean age 61.2 years).

Results showed that MACE occurred in 3.10 percent of patients treated with JAKi and 4.27 percent of those treated with TNFi, but the risk of MACE did not differ between the treatment arms (adjusted odds ratio [adjOR], 0.70, 95 percent confidence interval [CI], 0.43?1.16; p=0.17). [AIBD 2025, abstract S25]

Both JAKi and TNFi cohorts also showed similar risk of acute myocardial infarction (adjOR, 0.92, 95 percent CI, 0.41?2.03; p=0.84) and heart failure (adjOR, 0.76, 95 percent CI, 0.33?1.75; p=0.52), as well as cerebrovascular accident (adjOR, 0.6, 95 percent CI, 0.28?1.29; p=0.19).

Additionally, the risk of malignancy (adjOR, 0.6, 95 percent CI, 0.30?1.17; p=0.13), venous thromboembolism (adjOR, 0.82, 95 percent CI, 0.41?1.65; p=0.59), and all-cause mortality (adjOR, 0.66, 95 percent CI, 0.29?1.48; p=0.31) did not differ significantly between JAKi- and TNFi-treated patients.

In a subgroup of patients aged ≥65 years, those treated with either JAKi or TNFi also showed no significant difference in the risk of MACE, the researchers noted.

“Despite concerns about increased MACE risk with tofacitinib, our analysis did not reveal a higher CV risk for JAKi compared with TNFi in a CV risk-enriched population,” said the researchers.

“These findings suggest that JAKi and TNFi have a comparable CV safety profile, though continued monitoring in high-risk populations and prospective long-term studies are warranted to fully assess cardiovascular safety,” they noted.