Evidence map›Paper›PMID 39812549›Full record

ArticleAlimentary pharmacology & therapeutics2025

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Ronen Stein, Dan Turner, Séamus Hussey, Aysha Kawasmi, Oren Ledder, Jeremiah Levine, James Markowitz, Manar Matar, Esther Orlanski-Meyer, Richard K Russell and 4 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Alimentary pharmacology & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Observational
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Ronen SteinDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-4494-2388
Dan TurnerThe Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID https://orcid.org/0000-0001-5160-868X
Séamus HusseyNational Children's Research Center, University College Dublin and Royal College of Surgeons of Ireland, Dublin, Ireland.ORCID https://orcid.org/0000-0002-9362-0465
Aysha KawasmiThe Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Oren LedderThe Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Jeremiah LevineDivision of Pediatric Gastroenterology and Hepatology, New York University Langone Health, New York, New York, USA.
James MarkowitzThe Feinstein Institute for Medical Research, Northwell, Manhasset, New York, USA.
Manar MatarDivision of Gastroenterology, Hepatology, and Nutrition, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Esther Orlanski-MeyerThe Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Richard K RussellDivision of Pediatric Gastroenterology, The Royal Hospital for Children & Young People, Edinburgh, UK.
Ron ShaoulPediatric Gastroenterology Institute, Ruth Rappaport Children's Hospital, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel.
Anat Yerushalmy-FelerPediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Diane R MouldProjections Research, Phoenixville, Pennsylvania, USA.
Maire A ConradDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Funding

Identifying Genomic and Microbial Contributions in Early Childhood-Inflammatory Bowel DiseaseK23DK119585 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI CONRAD, MAIRE ABRAHAM · 2019 to 2023
$927k
ESPGHANEuropean Crohn's and Colitis OrganisationNIDDK NIH HHS K23 DK119585Takeda Pharmaceutical Company
6 · The paper itself

Abstract

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

aimsTo 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.

methodsWe 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.

resultsAt 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.

conclusionsDrug 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.

Indexed as

Antibodies, Monoclonal, HumanizedGastrointestinal AgentsInflammatory Bowel DiseasesAdolescentBayes TheoremBlood SedimentationChildChild, PreschoolC-Reactive ProteinDose-Response Relationship, DrugFemaleHumansMaleProspective StudiesRemission InductionTreatment OutcomeAntibodies, Monoclonal, HumanizedC-Reactive ProteinGastrointestinal AgentsvedolizumabdosingIBDpharmacokineticsvedolizumab

Identifiers

PMID39812549
PMCPMC11869157

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.