681 - Comparative Risk of Infections with Vedolizumab versus Ustekinumab in Anti-TNF Exposed Pediatric Patients with Inflammatory Bowel Disease

Publication Number: 4666.681

Ning Lyu, Brigham and Woman's hospital and Harvard-MIT center for Regulatory Science, Boston, MA, United States; Michaela Tracy, Boston Children's Hospital, Boston, MA, United States; Sebastian Schneeweiss, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, United States; Timothy Savage, Brigham and Women's Hospital / Boston Children's Hospital, Boston, MA, United States

Background: Treatment options for pediatric inflammatory bowel disease (IBD) have expanded in recent years, yet safe and effective choices remain limited after anti–tumor necrosis factor (anti-TNF) failure. Vedolizumab and Ustekinumab are increasingly used as second-line biologics in children with moderate to severe IBD, but comparative safety data, especially on infection risk, remain scarce.

Objective: To compare the risk of infections among pediatric patients with IBD treated with ustekinumab (exposure) versus vedolizumab (referent) after anti-TNF exposure.

Design/Methods: We conducted a retrospective cohort study using two nationwide U.S. commercial claims databases: Merative MarketScan Commercial Database (January 1, 2017–December 31, 2023) and Optum’s de-identified Clinformatics® Data Mart Database (January 1, 2016–May 31, 2025). Patients aged 6–18 years with Crohn disease or ulcerative colitis who initiated ustekinumab or vedolizumab following prior anti-TNF therapy were included. The index date was defined as the first prescription of either drug. Patients were followed until treatment discontinuation, outcome occurrence, treatment crossover, reaching 365 days or end of data availability.
Serious infection was defined as infection requiring hospitalization, and outpatient infection as an outpatient encounter requiring antimicrobial treatment within one day. Overlap weighting based on propensity scores balanced baseline covariates between groups. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for infection risk. Sensitivity analyses excluded serious gastrointestinal infections.

Results: A total of 770 children were included (ustekinumab: 383; vedolizumab: 387). After weighting, baseline characteristics were well balanced (standardized mean differences < 0.1). During a median follow-up of 316 days (IQR, 138–365), the incidence rate of serious infections was 29.0 per 100 person-years for ustekinumab and 49.1 for vedolizumab; outpatient infection rates were 333.3 and 347.8 per 100 person-years, respectively. The adjusted HR was 0.64 (95% CI, 0.24–1.69) for serious infection and 1.00 (95% CI, 0.66–1.52) for outpatient infection. Findings were consistent in sensitivity analyses.

Conclusion(s): Among pediatric patients with IBD and prior anti-TNF exposure, ustekinumab and vedolizumab were associated with similar risks of infections. These results provide real-world comparative safety evidence to support treatment decisions in children and adolescents with IBD.

Ning Lyu_CV
NingLyu_CV - 2025 - 10.pdf