Evidence map›Paper›PMID 38507036›Full record

Observational studyPaediatric drugs2024

The Effect of Polymorphisms and Other Biomarkers on Infliximab Exposure in Paediatric Inflammatory Bowel Disease: Development of a Population Pharmacokinetic Model.

Susana Clemente-Bautista, Iñaki F Trocóniz, Óscar Segarra-Cantón, Sara Salvador-Marín, Carlos J Parramón-Teixidó, Marina Álvarez-Beltrán, Luís A López-Fernández, Helena Colom, Maria J Cabañas-Poy, Maria Q Gorgas-Torner and 1 more

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Paediatric drugs, 2024. 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. Article
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  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

11 authors.

Susana Clemente-BautistaPharmacy Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035, Barcelona, Spain. susana.clemente@vallhebron.cat.ORCID http://orcid.org/0000-0001-6272-6438
Iñaki F TrocónizDepartment of Pharmaceutical Technology and Chemistry, Faculty of Pharmacy and Nutrition, University of Navarra, 31009, Navarra, Spain.
Óscar Segarra-CantónPaediatric Gastroenterology and Clinical Nutrition Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035, Barcelona, Spain.
Sara Salvador-MarínPharmacogenetics and Pharmacogenomics Laboratory, Pharmacy Department, Gregorio Marañón University Hospital, 28007, Madrid, Spain.
Carlos J Parramón-TeixidóPharmacy Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035, Barcelona, Spain.
Marina Álvarez-BeltránPaediatric Gastroenterology and Clinical Nutrition Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035, Barcelona, Spain.
Luís A López-FernándezPharmacogenetics and Pharmacogenomics Laboratory, Pharmacy Department, Gregorio Marañón University Hospital, 28007, Madrid, Spain.
Helena ColomPharmacy and Pharmaceutical Technology and Physical Chemistry Department, University of Barcelona, 08028, Barcelona, Spain.
Maria J Cabañas-PoyPharmacy Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035, Barcelona, Spain.
Maria Q Gorgas-TornerPharmacy Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035, Barcelona, Spain.
Marta MiaronsPharmacy Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035, Barcelona, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTherapeutic drug monitoring (TDM) of infliximab has been shown to be a effective strategy for inflammatory bowel disease (IBD). Population pharmacokinetic (PopPK) modeling can predict trough concentrations for individualized dosing.

objectiveThe aim of this study was to develop a PopPK model of infliximab in a paediatric population with IBD, assessing the effect of single nucleotide polymorphisms (SNPs) and other biomarkers on infliximab clearance.

methodsThis observational and ambispective single-centre study was conducted in paediatric patients with IBD treated with infliximab between July 2016 and July 2022 in the Paediatric Gastroenterology Service of the Hospital Universitari Vall d'Hebron (HUVH) (Spain). Demographic, clinical, and analytical variables were collected. Twenty SNPs potentially associated with variations in the response to infliximab plasma concentrations were analysed. infliximab serum concentrations and antibodies to infliximab (ATI) were determined by ELISA. PopPK modelling was performed using nonlinear mixed-effects analysis (NONMEM).

resultsThirty patients (21 males) were included. The median age (range) at the start of infliximab treatment was 13 years (16 months to 16 years). A total of 190 samples were obtained for model development (49 [25.8%] during the induction phase). The pharmacokinetics (PK) of infliximab were described using a two-compartment model. Weight, erythrocyte sedimentation rate (ESR), faecal calprotectin (FC), and the SNP rs1048610 (ADAM17) showed statistical significance for clearance (CL), and albumin for inter-compartmental clearance (Q). Estimates of CL1 (genotype 1-AA), CL2 (genotype 2-AG), CL3 (genotype 3-GG), Q, V

conclusionsA popPK model utilising weight, albumin, FC, ESR, and the SNP rs1048610 accurately predicted infliximab trough concentrations in children with IBD.

Indexed as

BiomarkersDrug MonitoringInflammatory Bowel DiseasesInfliximabPolymorphism, Single NucleotideAdolescentChildChild, PreschoolFemaleGastrointestinal AgentsHumansInfantMaleModels, BiologicalSpainBiomarkersGastrointestinal AgentsInfliximab

Identifiers

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Registered trials

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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.