Ustekinumab vs vedolizumab for older IBD patients: MACE not different, but mortality lower

In the real-world treatment of older adults with inflammatory bowel disease (IBD), the cardiovascular safety of ustekinumab is similar to that of vedolizumab, with no significant difference in the risk of major adverse cardiovascular events (MACE). However, ustekinumab is associated with a reduced risk of all-cause mortality.

Analysis of patient data from the TriNetX network showed that the incidence of MACE, the primary outcome, over a median follow-up of 3.1 years was comparable between ustekinumab- and vedolizumab-treated patients in both the ulcerative colitis (UC) (10.3 percent vs 12.2 percent; adjusted hazard ratio [aHR], 0.884, 95 percent confidence interval [CI], 0.743–1.052; p=0.164) and Crohn’s disease (CD) (10.5 percent vs 11.6 percent; aHR, 0.919, 95 percent CI, 0.803–1.050; p=0.214) cohorts, reported lead investigator Dr Emily Chan from Louis A Weiss Memorial Hospital in Chicago, Illinois, US. [Chan E, et al, CCC 2025]

However, the cumulative risk of all-cause mortality was significantly lower with ustekinumab than with vedolizumab in both the UC (2.4 percent vs 4.9 percent; aHR, 0.536, 95 percent CI, 0.389–0.738; p=0.0001) and CD (2.9 percent vs 3.9 percent; aHR, 0.770, 95 percent CI, 0.603–0.983; p=0.036) cohorts, Chan said.

Additionally, ustekinumab-treated patients with UC were less likely to have venous thromboembolism (VTE) (4.2 percent vs 5.8 percent; aHR, 0.769, 95 percent CI, 0.592–0.999; p=0.049) and undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (2.9 percent vs 4.3 percent; aHR, 0.703, 95 percent CI, 0.515–0.961; p=0.026) than those who received vedolizumab.

Lower VTE risk a boon in UC

The findings suggest that “while no differences in overall MACE were observed, ustekinumab may offer better cardiovascular safety,” according to Chan. This may hold clinical implications, given the “lack of treatment guidelines tailored to older adults, who make up <5 percent of participants in IBD clinical trials.” [Gastroenterology 2022;163:8-13]

The protective effect of ustekinumab against VTE is of particular importance due to the heightened risk of VTE among older patients with IBD, especially those with UC, she continued. [Inflamm Bowel Dis 2020;26:1761-1768]

However, it is crucial to acknowledge that other therapies could influence VTE risk, according to Chan. A multicentre study of 301 UC patients who had undergone colectomy for medically refractory disease showed a higher rate of early VTE with preoperative exposure to anti-TNF alpha agents (p=0.047) and of late VTE with preoperative exposure to vedolizumab (p=0.03) relative to tofacitinib and ustekinumab. [Am J Gastroenterol 2024;119:1525-1535]

“Clinicians should consider cardiovascular risks when prescribing biologics,” she said.

The study included propensity-score matched 2,286 ustekinumab users and 2,286 vedolizumab users in the UC cohort and 3,862 ustekinumab users and 3,862 vedolizumab users in the CD cohort. These patients were at least 50 years of age.

Chan acknowledged several limitations to the study, including the potential for residual confounding and the lack of endoscopic or histologic data.