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Record W4388799076 · doi:10.1016/j.gastha.2023.11.004

Body Surface Area-Based Dosing of Infliximab is Superior to Standard Weight-Based Dosing in Children With Very Early Onset Inflammatory Bowel Disease

2023· article· en· W4388799076 on OpenAlexafffund
Lorraine Stallard, Karen Frost, Nathaniel Frost, Luca Scarallo, Eric I. Benchimol, Thomas D. Walters, Peter Church, Anne M. Griffiths, Aleixo M. Muise, Amanda Ricciuto

Bibliographic record

VenueGastro Hep Advances · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsHospital for Sick ChildrenUniversity of TorontoInstitute for Clinical Evaluative SciencesSickKids Foundation
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesCanadian Institutes of Health ResearchCanada Research ChairsLeona M. and Harry B. Helmsley Charitable Trust
KeywordsDosingInfliximabMedicineInflammatory bowel diseaseBody surface areaBody weightInternal medicineGastroenterologyDisease

Abstract

fetched live from OpenAlex

Background and AimsChildren with very early onset inflammatory bowel disease (VEO-IBD) are uniquely at risk of inadequate infliximab (IFX) exposure. We studied the association between standard body weight (BW)-based and body surface area (BSA)-based dosing strategies and outcomes.MethodsWe identified VEO-IBD patients treated with IFX before 9 years at a single center. Patients were separated into those that received a BSA-based dose (200 mg/m2) and standard BW dosing (5 mg/kg). IFX drug levels, dose intensification, time on steroids, and long-term outcomes were compared. Receiver operator characteristic curves determined the optimal BW- and BSA-based dose to achieve a trough ≥10 μg/ml at dose 4 (IFX#4).ResultsForty-three children with VEO-IBD were identified. Receiver operator characteristic curves demonstrated optimal BW- and BSA-based doses to achieve IFX trough ≥10 μg/ml at IFX#4 were 7.5 mg/kg and 180mg/m2. Children were classified to standard BW dosing (22/43) and BSA dosing (10/43). IFX#4 trough was significantly higher in those who received BSA dosing (BSA 18.6 μg/ml [interquartile range 10.8–28.1] vs BW 5.1 μg/ml [interquartile range 2.6–10.7], P = .04). BSA dosing was more likely to achieve a target drug level >10 μg/ml at IFX#4 (BSA 70% vs BW 18%, P = .02). BW dosing was associated with a greater likelihood of dose escalation (BW 82% vs BSA 30%, P < .01) and a shorter time to first escalation. BSA dosing was associated with shorter time spent on steroids (P = .02).ConclusionYoung children require higher IFX dosing to achieve adequate drug exposure. Our data support the use of a BSA-based dose of 200 mg/m2 or, if a BW-based approach is used, 7.5 mg/kg. BSA dosing allows the use of a consistent dose over the age and weight spectrum. Children with very early onset inflammatory bowel disease (VEO-IBD) are uniquely at risk of inadequate infliximab (IFX) exposure. We studied the association between standard body weight (BW)-based and body surface area (BSA)-based dosing strategies and outcomes. We identified VEO-IBD patients treated with IFX before 9 years at a single center. Patients were separated into those that received a BSA-based dose (200 mg/m2) and standard BW dosing (5 mg/kg). IFX drug levels, dose intensification, time on steroids, and long-term outcomes were compared. Receiver operator characteristic curves determined the optimal BW- and BSA-based dose to achieve a trough ≥10 μg/ml at dose 4 (IFX#4). Forty-three children with VEO-IBD were identified. Receiver operator characteristic curves demonstrated optimal BW- and BSA-based doses to achieve IFX trough ≥10 μg/ml at IFX#4 were 7.5 mg/kg and 180mg/m2. Children were classified to standard BW dosing (22/43) and BSA dosing (10/43). IFX#4 trough was significantly higher in those who received BSA dosing (BSA 18.6 μg/ml [interquartile range 10.8–28.1] vs BW 5.1 μg/ml [interquartile range 2.6–10.7], P = .04). BSA dosing was more likely to achieve a target drug level >10 μg/ml at IFX#4 (BSA 70% vs BW 18%, P = .02). BW dosing was associated with a greater likelihood of dose escalation (BW 82% vs BSA 30%, P < .01) and a shorter time to first escalation. BSA dosing was associated with shorter time spent on steroids (P = .02). Young children require higher IFX dosing to achieve adequate drug exposure. Our data support the use of a BSA-based dose of 200 mg/m2 or, if a BW-based approach is used, 7.5 mg/kg. BSA dosing allows the use of a consistent dose over the age and weight spectrum.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.043
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.226
Teacher spread0.222 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations12
Published2023
Admission routes2
Has abstractyes

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