P533 Ustekinumab therapeutic drug monitoring in Crohn’s disease patients with loss of response
Bibliographic record
Abstract
Crohn’s disease (CD) patients on ustekinumab (UST) may experience a partial or secondary loss of response (LOR). The aim of the study was to assess the role of UST therapeutic drug monitoring (TDM) in patients with a LOR. In this prospective study, trough UST TDM was performed in CD patients experiencing either a partial response or a secondary LOR to UST based on clinical (HBI ≥5) and/or objective inflammation (CRP ≥5 or FCP ≥250 or SES-CD >2). Patients were treated at the discretion of the physician prior to the UST TDM results becoming available. Patients were reassessed for complete remission (HBI <5, CRP <5 and FCP < 250) or for response (HBI decrease by >3 points and a 50% decrease in CRP, FCP). UST drug and antibody concentrations were assessed using a liquid phase assay (Prometheus Laboratories Inc.). 38 instances of clinical LOR were identified in 35 patients. The median age at LOR was 39 years (range 18–72), 57% were male and 91% were biologic experienced. The median follow-up visit occurred at 3.8 months (IQR 3.1–4.4 months). Treatment interventions and outcomes are listed in Table 1. When UST was dose escalated with q 4 week dosing or re-induction, patients with active inflammation achieved complete remission and response in 38% and 31%, respectively. When baseline TDM was available (n = 35), the mean UST concentration was significantly lower in patients with active biochemical or endoscopic inflammation (n = 31) compared with patients with no objective inflammation (n = 4): 5.21 vs. 18.74 μg/ml, p < 0.0001. In the 27 patients with active inflammation in whom UST treatment was continued (29 instances), the mean baseline UST concentration was higher in patients who achieved complete remission (n = 10), compared with those who did not (n = 19): 7.61 vs. 4.01 μg/ml, p = 0.01. The mean baseline FCP was significantly lower in patients who achieved complete remission, compared with patients who did not (414 vs. 993 μg/g, p = 0.03). The mean post treatment UST drug concentration was significantly higher in patients who achieved complete remission (n = 8), compared with those who did not achieve complete remission (n = 14): 13.04 vs. 8.57 μg/g, p = 0.03. Treatment intervention and outcomes. Overall, ustekinumab dose escalation or reinduction in CD patients with a LOR resulted in complete remission or response in 69% of patients. Baseline higher drug concentrations and low FCP were associated with significantly increased rates of complete remission. Higher post-treatment drug concentrations were significantly associated with increased rates of complete remission.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".