Ustekinumab versus vedolizumab and ustekinumab versus tumor necrosis factor alpha agent infectious adverse effects in patients with ulcerative colitis, a real-world data study.

INTRODUCTION: Ulcerative colitis (UC) often requires immunomodulatory therapies that balance efficacy with safety. Among biologics, vedolizumab and ustekinumab have emerged as alternatives to anti-tumor necrosis factor alpha (TNF-α) agents. We aim to address the incidence of specific infectious adverse events associated with these agents outside clinical trials using a real-world database.

METHODS: We conducted a retrospective cohort study using the TriNetX database. Three cohorts were defined as adult patients with UC, each treated with one of the following: ustekinumab, anti-TNFα agents, or vedolizumab. We used propensity score matching to balance groups. Outcomes included a new infection diagnosis.

RESULTS: Participants receiving ustekinumab demonstrated a significantly lower risk of several infections compared to those on anti-TNFα therapy, including pneumonia, urinary tract infection, cellulitis, Clostridioides difficile infection, infectious diarrhea, and sepsis. Compared to vedolizumab, ustekinumab was associated with a reduced risk of cellulitis and Clostridioides difficile infection.

DISCUSSION: Our findings demonstrate that ustekinumab is associated with a significantly lower risk of several infections. However, there is a less prominent difference in infectious risk when compared to vedolizumab. These results suggest that ustekinumab may offer a safer alternative, compared to anti-TNFα agents and possibly to vedolizumab, particularly those at higher risk of infections.