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Record W3007144917 · doi:10.1093/jcag/gwz047.103

A104 A STUDY OF POST-INDUCTION INFLIXIMAB TROUGH LEVELS DEMONSTRATES MOST PEDIATRIC IBD PATIENTS ARE BEING UNDERDOSED

2020· article· en· W3007144917 on OpenAlexaffabout
Farah Faytrouni, Rachel E. Harris, Sally Lawrence, R C G Russel

Bibliographic record

VenueJournal of the Canadian Association of Gastroenterology · 2020
Typearticle
Languageen
FieldMedicine
TopicPharmaceutical studies and practices
Canadian institutionsBC Children's Hospital
Fundersnot available
KeywordsMedicineInfliximabCohortTrough levelInternal medicineRegimenTrough ConcentrationTherapeutic drug monitoringGastroenterologySurgeryPharmacokineticsDisease

Abstract

fetched live from OpenAlex

Abstract Background Infliximab (IFX) is widely used for induction and maintenance of remission in pediatric inflammatory bowel disease (PIBD). Post induction IFX trough levels are a predictor of clinical and biochemical remission at week 52. Aims - evaluate the effectiveness of infliximab (IFX) induction regimens in attaining therapeutic post induction IFX trough levels in 2 PIBD cohorts. - investigate baseline laboratory values and patient factors as predictors of post-induction levels. Methods 78 patients from Vancouver, Canada [Cohort 1 (C1) originator IFX; variable dose induction regimen] and 62 patients from Glasgow, Scotland [Cohort 2 (C2) replication cohort - biosimilar IFX; standard induction of 5mg/kg at 0, 2 and 6 weeks, with 8 weekly maintenance] were included in the study. Baseline characteristics and laboratory values from time of IFX initiation were recorded. Mann-Whitney U Testing was utilized to analyse the relationship between IFX trough levels and lab parameters. Results The median pre-dose 4 trough in C1 & C2 was 4.25mg/L (IQR 7.8) and 1.85mg/L (IQR 3.38) respectively. In C1 patients who had a trough level <3mg/L pre-dose 4, 62% (20/32) had already had a dose adjustment documented. The IFX dose of 50% (39/78) of C1 patients and 65% (40/62) of C2 patients was escalated following the pre-dose 4 IFX level. TABLE 1 Baseline median albumin (Alb) was significantly lower and replicated in both cohorts in those with low pre-dose 4 IFX levels: IFX trough <0.8mg/L C1: Alb 30g/L vs 37.5g/L in IFX ≥0.8mg/L, p=0.002 C2: Alb 34.5g/L vs 37g/L in IFX ≥0.8mg/L, p=0.02 IFX trough <3.0mg/L C1:Alb 34.5g/L vs 38g/L in IFX ≥3.0mg/L, p= 0.05 C2:Alb 35g/L vs 37g/L in IFX ≥3.0mg/L, p=0.04 IFX trough <5.0mg/L C1:Alb 35g/L vs 39g/L in IFX ≥5.0mg/L, p=0.006 C2:Alb 35g/L vs 37g/L in IFX ≥5.0mg/L, p=0.45 In the combined cohort (C1 + 2), patients with baseline albumin ≤30g/L had significantly lower IFX levels pre-dose 4 than those with albumin >30g/L (1.4mg/L vs 3.55mg/L, p=0.0003). In patients with an albumin ≤30g/L, 23% (6/26) achieved a dose 4 trough level of ≥3.0mg/L, however only 1/6 patients received a standard induction regime meaning only 4% (1/26) of patients had a trough ≥3.0mg/L on standard treatment. Conclusions Standard IFX induction regimen is ineffective in achieving relevant post-induction trough levels (>5 mg/L) in the majority of PIBD patients regardless of IFX type. We suggest that optimization of initial IFX prescribing based on baseline albumin (i.e. a higher dose given to patients with albumin < 30g/L) and subsequent levels will improve post-induction trough levels and consequently clinical outcomes for a greater proportion of patients. Funding Agencies None

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.034
Threshold uncertainty score0.982

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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 head0.037
GPT teacher head0.289
Teacher spread0.251 · 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.

The models applied no category: nothing in the taxonomy fit this work.
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".

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Citations0
Published2020
Admission routes2
Has abstractyes

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