Covariates Influencing the Exposure-Response Relationship for Certolizumab Pegol During the Induction and Maintenances Phases in Patients with Crohnʼs Disease
Bibliographic record
Abstract
Introduction: Therapeutic drug monitoring during induction ofcertolizumab pegol (CZP) therapy for Crohn's disease (CD) may be a useful tool to predict efficacy outcomes.This analysis examined the effects of covariates that may influence the exposure-response relationship of CZP at the end of induction (Week 6) and maintenance (Week 26) using a previously described population pharmacokinetic model.1Figure 2Methods: Data were available from 2157 adults with moderate to severe CD who were treated with CZP in 1 of 9 trials. Multiple backward logistic regression was carried out to identify covariates associated with outcome to CZP therapy, including age, gender, weight, CZP concentration (log-transformed), antibodies to CZP (categorical), prior anti-TNF treatment, immunomodulator use, disease duration, prior surgery, baseline hematocrit, albumin, C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI).Endpoints at Weeks 6 and 26 included clinical remission (CDAI plus FC ≤250 μg/g (composite endpoint). Drop-outs were considered failures. Receiver operating characteristic (ROC) analyses were carried out to determine optimal CZP concentrations for various endpoints. Results: CZP concentrations at Week 6 were significantly associated with all Week 6 outcomes (Figure 1a) and the composite outcome at Week 26. CZP concentration at Week 12 was significantly associated with FC ≤250 μg/g and the composite outcome at Week 26 (Figure 1b). Other covariates were significantly associated with various endpoints (Table 1). Youden index thresholds of 36 μg/mL and 15 μg/mL at Week 6 and Week 12, respectively, were associated with Week 6 and 26 outcomes in ROC analyses (Table 2). Thresholds of 44 μg/mL and 48 μg/mL at Week 6 were associated with 90% specificity of achieving CRP ≤5 mg/L or FC ≤250 μg/g and with CDAI remission or the composite endpoint, respectively, at Week 6.Figure 1Conclusion: CZP concentrations at the end of induction and during maintenance are significantly associated with clinically meaningful endpoints at the end of induction and maintenance. Achieving the threshold CZP concentrations may increase the likelihood of attaining these outcomes.Figure 3
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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 | 0.007 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".