S1637 Ustekinumab vs Vedolizumab and Ustekinumab vs Tumor Necrosis Factor Alpha Agent Infectious Adverse Effects in Patients With Ulcerative Colitis: A Short Report Based on Real-World Data

Introduction: Ulcerative colitis (UC), a chronic inflammatory bowel disease affecting the colon, 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 regarding demographics, comorbidities, body mass index, and the use of other immunosuppressive medications. Outcomes included a new diagnosis of pneumonia, urinary tract infections, cellulitis, shingles, meningitis, Clostridioides difficile infection, or sepsis. Results: After propensity score matching, 11,228 participants were included in each cohort comparing ustekinumab- and anti-TNFα-treated individuals, and 11.576 participants were included in each cohort comparing ustekinumab- and vedolizumab-treated individuals. Participants receiving ustekinumab demonstrated a significantly lower risk of several infections compared to those on anti-TNFα therapy, including pneumonia with an odds ratio (OR) of 0.72 (95% CI 0.58–0.89), any urinary tract infection OR 0.64 (95% CI 0.53–0.78), cellulitis OR 0.61 (95% CI 0.50–0.74), Clostridioides difficile infection OR 0.74 (95% CI 0.62–0.89), infectious diarrhea OR 0.63 (95% CI 0.47–0.85), and sepsis OR 0.70 (95% CI 0.577–0.842). Compared to vedolizumab, ustekinumab was associated with a reduced risk of cellulitis OR 0.77 (95% CI 0.62, 0.95) and Clostridioides difficile infection OR 0.80 (95% CI 0.67–0.95). However, no significant difference was detected for the risk of other infections. Conclusion: Our findings demonstrate that ustekinumab is associated with a significantly lower risk of several infections and even severe infectious processes within one year when compared with anti-TNFα; however, there is a less prominent difference in infectious risk between vedolizumab and anti-TNFα agents. 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.