P460 Early use of therapeutic drug monitoring to individualize infliximab therapy in paediatric IBD: a multicentre prospective COHORT study
Bibliographic record
Abstract
Background: Therapeutic drug monitoring (TDM) during infliximab (ifx) maintenance therapy is regularly used in Canada to assess loss of response and to aid in dose optimization, with pre-infusion trough levels in the range of 5–10ug/ml recommended as targets. Levels achieved early following standard induction dosing among pediatric patients are highly variable, and often inadequate even at week 12. Limited data exist in adults or children concerning the role of TDM and target levels during induction. Within the Canadian children IBD Network, we proposed to measure ifx levels during induction, aiming to determine the optimal levels required to achieve target 5–10 ug/ml at the start of maintenance. Methods: Beginning in May 2016, children initiating ifx at SickKids Hospital and at other centres within the CIDsCANN inception cohort study had trough levels measured by ELISA at the time of the of final induction and first maintenance infusions (doses 3 and 4). Induction regimens were at the discretion of the treating physician, but often intensified among patients with severe UC. Influence of patient demographics and baseline disease activity (PGA, wPCDAI/PUCAI) on early trough levels were assessed. Results: From May to December 2016 at 9 participating sites, 66 children (median age 11.8 years, 53% male, 52% CD, 48% UC/IBD-U; IBD duration at start of biologic 4.3mos (IQR 14.02–13.02 mos). Induction regimen was “standard” (0, 2, 6 weeks) in 77% and intensified in 23% (O, 1, 4 weeks; all steroid refractory colitis). Table 1 gives characteristics of those receiving standard vs intensified regimens As shown in Table 1, IFX levels were highly variable prior to 3rd induction dose. Within the standard induction dosing cohort, the interval between dose 3 and 4 was shortened to 6 weeks in 50%. 41% attained targeted 5–10 dose 4 levels. Despite higher dosing per kg during induction and shorter interval prior to dose 4 in the intensified regimen, IFX levels at start of maintenance were comparable to patients receiving standard induction. Table 1. Basic demographic data Induction Infliximab TDM Study Conclusions: Variability in infliximab exposure is evident during induction. Adjusting dose intervals based on pre 3rd dose induction levels, increases the likelihood of entering maintenance dosing on target. An intensified regimen is necessary for patients with active colitis to achieve comparable post induction levels. The results suggest that the use of TDM during induction to individualize dosing more consistently ensures adequate drug exposure at start of maintenance.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".