Off-Label Ustekinumab and Vedolizumab in Pediatric Anti-TNFα Refractory IBD: Therapeutic Drug Monitoring Insights from a Case Series

TL;DR

This study explores the use of two drugs in children with severe IBD who don't respond to standard treatment, highlighting the value of monitoring drug levels to guide therapy.

Contribution

The study provides insights into therapeutic drug monitoring for off-label use of ustekinumab and vedolizumab in pediatric IBD patients.

Findings

Clinical improvement often correlated with drug concentrations above adult reference ranges, but this varied between patients.

One patient remained stable despite undetectable drug levels and high anti-drug antibodies, showing significant individual variability.

Therapeutic drug monitoring helped interpret pharmacokinetic and immunogenic differences, supporting personalized treatment decisions.

Abstract

Background: Vedolizumab and ustekinumab are increasingly used off-label in pediatric inflammatory bowel disease (IBD) unresponsive or refractory to anti–TNFα therapy. Despite their increasing use in clinical practice, evidence in the pediatric population remains limited, especially regarding therapeutic exposure thresholds and the clinical utility of therapeutic drug monitoring (TDM). Methods: We report a series of five pediatric cases with Crohn’s disease or ulcerative colitis treated with ustekinumab or vedolizumab after anti-TNFα failure. Trough drug concentrations, anti-drug antibodies (ADAs), clinical scores (PCDAI/PUCAI), biomarkers (fecal calprotectin, C-reactive protein), and endoscopic findings were assessed longitudinally. Results: In all cases, we observed recurrent discordance between clinical indices (PCDAI/PUCAI), biochemical markers, and endoscopic activity. Clinical improvement frequently correlated with trough concentrations above commonly cited adult-derived reference ranges (>15 µg/mL for vedolizumab; >3 µg/mL for ustekinumab), although this alignment was not uniform across patients. Notably, one patient developed high-titre ADAs with undetectable ustekinumab levels, yet remained clinically stable, suggesting substantial interindividual variability in pharmacokinetics, immunogenicity, and disease control. Conclusions: Ustekinumab and vedolizumab are promising off-label options for pediatric refractory IBD. In this case series, TDM contributed to the interpretation of pharmacokinetic variability and immunogenicity, offering contextual insights that may support dose adjustments and therapeutic decision-making. Integrating TDM with clinical, biochemical, and endoscopic monitoring may improve optimize individualized treatment in this complex and vulnerable patient group.

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