P561 Impact of ustekinumab TDM on clinical practice: a multi-centre, prospective, cross-sectional observational trial—mUST-Decide
Bibliographic record
Abstract
Therapeutic drug monitoring (TDM) is an important part of the management of biologics used in the treatment of IBD. Current understanding of ustekinumab (UST) TDM is limited and its value in clinical practice is unknown. We hypothesised that addition of UST TDM to clinical practice would alter clinical decisions in the treatment of Crohn’s disease (CD). We enrolled 112 consecutive UST-treated CD patients across 11 sites in Canada from April 2017 to January 2018. HBI, CRP, baseline characteristics and clinical decisions were recorded for 110 subjects at the single study visit, faecal calprotectin (FCP) was performed (local lab, standard of care) and blood was drawn for TDM (Sanquin, UST RIA). TDM results were provided at the end of the study, and sites recorded a hypothetical clinical decision with UST TDM ± FCP. Congruency of the actual (D1) and hypothetical decisions (D2 (clinical + TDM), D3 (clinical +TDM and FCP)) were assessed using McNemars paired χ2 test. A four- member expert panel examined all cases (3 experts/case) and made decisions by majority consensus – all D1 first, then all D2, then all D3. Experts were provided with additional training on UST PK data and interpretation, but decisions were not protocolised. Patients enrolled in the study were highly refractory (90% aTNF exposed, median 16.2 years of CD) but 70% were in clinical remission (HBI <5). At a population level, no differences could be detected before and after the introduction of TDM alone (p = 1.0), or TDM + FCP (p = 0.86). However, at a patient level, 39% of D2 decisions changed and 50% of D3 changed (see table). Examining the expert panel decisions at a population level, no differences could be detected before and after the introduction of TDM alone (p = 0.16), while decisions with TDM + FCP were significantly different (p = 0.0006). At the patient level with TDM alone, 23% of individual decisions changed and 67% of decisions were different when incorporating TDM + FCP. No new safety signal was observed, no patient samples were positive for ADAb to UST. Table. Summary of clinical decisions at a population and patient level. At a population level, introduction of UST TDM into routine clinical practice did not significantly impact clinical decisions for clinicians or experts, but adding FCP significantly altered clinical decisions for experts, but not clinicians. The divergence in impact of TDM and FCP between clinicians vs. experts highlights a need for greater education. Further study to clarify the use and impact of these tests in a proactive setting is warranted.
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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 | 0.006 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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.
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".