P337 Early infliximab clearance predicts remission in children with Crohn’s Disease
Bibliographic record
Abstract
Abstract Background Recent studies suggest pediatric Crohn’s Disease (CD) patients have higher infliximab clearance (IFX CL) for body weight and lower serum IFX when dosing by weight. Our aim was to determine if IFX CL calculated based on therapeutic drug monitoring (TDM) data predicts long term outcome. Methods Retrospective study of CD patients seen at the Stollery Children’s hospital from Jan 2013-Jul 2019. Anthropometric, lab, IFX TDM & disease data were collected for those having >2 serum IFX levels. IFX CL was calculated using non linear mixed effects modelling. The data was fit to a 2-compartment model with linear elimination. Outcomes were defined at 4, 9 & 15 months. Remission is defined as wPCDAI<12.5, CRP<4 & steroid-free for 4 months. Subjects that underwent intestinal surgery or ceased IFX due to refractory CD are non-responders. Logistic regression was used to determine early predictors (at baseline or end of induction) associated with remission at 4, 9 & 15 months. The variables evaluated were: IFX CL, IFX trough level, sex, age, PARIS classification, CRP, ESR, Alb, Hgb, weight, BSA, BMI, previous anti-TNF & immunomodulator use. Results 85 subjects were included, with a median follow up of 670 days (IQR: 304,1105). See table 1 for baseline characteristics. Regression analysis showed early IFX CL was the only significant early predictor of remission for every timepoint. Baseline IFX CL and end of induction IFX CL, measured in L/h, were associated with 15-month remission with an OR of 0.606 (95%CI: 0.394,0.931; p=0.022) and 0.373 (95%CI: 0.207,0.669; p=0.001) respectively. Similar results obtained at 4 & 9 months. ROC analysis of remission was done using only early IFX CL. A baseline IFX CL of 5.83 L/h predicted 15-month remission with a sensitivity & specificity of 0.649 & 0.667 (AUC=0.701). End of induction IFX CL of 6.06 L/h predicted 15-month remission with a sensitivity & specificity of 0.676 & 0.611 (AUC=0.709). Similar results obtained at 4 & 9 months. Conclusion In all timepoints, early IFX CL was a strong predictor of later remission compared to dose intensity, frequency, IFX levels and wPCDAI & CRP at end of induction. This suggests early IFX CL is a marker of early biological response to IFX. Early dose optimization is required in those with high IFX CL to ensure optimal response with adequate drug exposure. This will facilitate early change in treatment for those with inadequate response.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".