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Record W2912175184 · doi:10.1093/ecco-jcc/jjy222.609

P485 Prediction Model Incorporating Pharmacokinetics Calculates Probability of Endoscopic Healing in Patients with ulcerative colitis Starting Infliximab Therapy

2019· article· en· W2912175184 on OpenAlexaff
Niels Vande Casteele, Vipul Jairath, Jenny Jeyarajah, Parambir S. Dulai, Siddharth Singh, Brian G. Feagan, William J. Sandborn

Bibliographic record

VenueJournal of Crohn s and Colitis · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsWestern UniversityRobarts Clinical Trials
Fundersnot available
KeywordsMedicineInfliximabUlcerative colitisConfidence intervalLogistic regressionWhite blood cellPharmacokineticsPopulationInternal medicineEndoscopyArea under the curveGastroenterologySurgeryTumor necrosis factor alpha

Abstract

fetched live from OpenAlex

Infliximab (IFX) is effective treatment for moderate to severe ulcerative colitis (UC), however baseline parameters associated with, and probability of achieving endoscopic healing during induction and maintenance therapy are unknown. Data from the ACT-1 and -2 trials encompassing 484 IFX-treated UC patients were analysed. A two-compartment population pharmacokinetic model was used to calculate baseline IFX clearance (CL). The Mayo endoscopic score was available at Weeks (W) 0, 8 and 30. Three logistic regression prediction models were developed using the ACT-1 dataset and externally validated using the ACT-2 dataset. The models evaluated W0 variables for prediction of endoscopic healing (MES ≤ 1) at W8 and W30, and W8 variables for prediction of endoscopic healing at W30. An online tool to calculate the probability of achieving endoscopic healing in individual patients was also created. IFX CL, stool frequency, and rectal bleeding at W0 were independently associated with endoscopic healing at W8 with an area under the curve (AUC [95% confidence interval]) of 0.73 (0.66–0.79) and 0.67 (0.60–0.74) for the derivation and validation models, respectively. IFX CL, stool frequency, white blood cell count, and weight at W0 were independently associated with achieving endoscopic healing at W30 with an AUC of 0.68 (0.62–0.75) and 0.67 (0.61–0.74) for the derivation and validation models, respectively. Rectal bleeding, stool frequency, white blood cell count, and albumin at W8 were independently associated with achieving endoscopic healing at W30 with an AUC of 0.83 (0.78–0.89) and 0.78 (0.72–0.84), for the derivation and validation models, respectively. Odds ratios for the factors predictive of endoscopic healing are shown in Table 1. Table 1. Odds ratios for W0 and W8 factors predictive of endoscopic healing in patients receiving IFX. Variable selection was based on univariable selection (p < 0.15) followed by a forward stepwise multi-variable logistic regression model (p < 0.1). Patient-level probabilities for endoscopic healing at W8 and/or W30 can be calculated using a free online tool available at http://premedibd.com. The predicted probability of endoscopic healing at W8 for a hypothetical UC patient starting IFX therapy using the online tool is shown in Figure 1. Figure 1. Probability of W8 endoscopic healing in a hypothetical UC patient. A population pharmacokinetic model uses sex and albumin to calculate W0 IFX CL, which is incorporated into the prediction model with stool frequency and rectal bleeding. Three models were developed and externally validated to calculate the probability of endoscopic healing in individual patients with UC during IFX induction and/or maintenance therapy based on IFX CL, patient demographics and disease activity measures at W0 and/or W8.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.011
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.011
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0040.001

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 head0.008
GPT teacher head0.237
Teacher spread0.229 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
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
Published2019
Admission routes1
Has abstractyes

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