Aliment Pharmacol Ther. 2025 Mar;61(6):1000-1010.doi: 10.1111/apt.18484. Epub 2025 Jan 15.

Ronen Stein ^1 2, Dan Turner ³, Séamus Hussey ⁴, Aysha Kawasmi ³, Oren Ledder ³, Jeremiah Levine ⁵, James Markowitz ⁶, Manar Matar ⁷, Esther Orlanski-Meyer ³, Richard K Russell ⁸, Ron Shaoul ⁹, Anat Yerushalmy-Feler ¹⁰, Diane R Mould ¹¹, Maire A Conrad ^1 2

Author information

¹Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

²Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

³The Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.

⁴National Children's Research Center, University College Dublin and Royal College of Surgeons of Ireland, Dublin, Ireland.

⁵Division of Pediatric Gastroenterology and Hepatology, New York University Langone Health, New York, New York, USA.

⁶The Feinstein Institute for Medical Research, Northwell, Manhasset, New York, USA.

⁷Division of Gastroenterology, Hepatology, and Nutrition, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

⁸Division of Pediatric Gastroenterology, The Royal Hospital for Children & Young People, Edinburgh, UK.

⁹Pediatric Gastroenterology Institute, Ruth Rappaport Children's Hospital, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel.

¹⁰Pediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

¹¹Projections Research, Phoenixville, Pennsylvania, USA.

Abstract

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior. We employed the model for exposure-response evaluation and for investigating doses in paediatric patients to match the adult exposure at the labelled dose.

Results: At Week 30, 104/129 (81%) children (53% female and 47% Crohn disease) remained on vedolizumab, of whom 39 (31%) in the exposure-response evaluation were in deep biochemical remission. Increased baseline drug clearance was associated with lower deep biochemical remission rates at Week 30 based on ESR/CRP (OR 0.47 [95% CI 0.2-1.05, p = 0.08]) and calprotectin < 100 μg/g (OR 0.13 [95% CI 0.1-0.79, p < 0.05]). Higher weight and lower serum albumin were associated with increased clearance (p < 0.001). Simulation models found that, for children ≤ 30 kg, tiered fixed dosing regimens best matched adult drug concentrations.

Conclusions: Drug clearance was strongly influenced by serum albumin. Baseline clearance predicted deep biochemical remission at Week 30. Further investigation is needed to better understand optimal dosing strategies-especially for lower-weight children receiving vedolizumab.