DOP58 IdeaL: a multi-centre prospective infliximab dose to level pharmacokinetic study during induction in paediatric Crohn’s disease
Notice bibliographique
Résumé
Infliximab (IFX) is an effective therapy for Crohn's disease (CD), but pharmacokinetic data during induction are sparse. The objective of this study was to model the pharmacokinetic (PK) and use individual clearance (CL) estimates to explore relationships between PK and clinical remission in children with CD receiving IFX induction. A prospective study was conducted at 3 Canadian Children IBD Network sites. Baseline data collected included simple endoscopic score (SES-CD) and weighted Paediatric CD Activity index (wPCDAI). IFX doses ranged 5 to 10 mg/kg. Up to 8 IFX levels per subject were collected: trough and peak at doses 2 and 3, trough prior dose 4, between doses 3 and 4, and trough prior to dose 5. Free antibody to IFX (ATI) levels measured at doses 3, 4, and 5. Faecal calprotectin (FCP), wPCDAI, CBC, albumin (ALB), ESR, and CRP samples were also collected at each dose. NONlinear Mixed Effects Modelling was used to develop a population PK model using standard model building approaches. Covariate factors had to be significant at p < 0.001 and clinically relevant (>20% change in CL) to be retained. Dose and frequency may be adjusted clinically or based on preceding trough levels. Thirty-five subjects, 18 males, were recruited and followed for up to 22 weeks over 5 doses. Median age was 12.3 years (IQR: 10.2–14.8). Median dose for Dose 1 was 6.0 mg/kg (IQR: 5.0–7.0) and increased to 7.0 mg/kg (IQR: 5.0–8.3) for Dose 5. Eighty per cent of patients did not follow the standard induction and maintenance regimen of 0, 2, 6, and 14 weeks. Dose 4 had the most variability in frequencies with the median of Q6W. IFX CL was marked varied between subjects and improved during follow-up. Median baseline CL was 0.31 (IQR: 0.24,0.40). During single covariate evaluations, the following factors were identified as potentially predictive of IFX CL: ALB (negative correlation) and FCP, CRP, SES-CD, wPCDAI, and ESR (positive correlation). On back elimination, only ALB and CRP were important predictors. CL had a nonlinear correlation with weight where CL/kg was higher in those weigh < 30 kg vs. those >30 kg (p = 0.005). Twenty-nine subjects (83%) went into complete remission (wPCDAI <12.5). IFX CL of ≤0.39 l/day was a good predictor of remission status determined by wtPCDAI at Dose 5 (AUC [95% CI] = 0.828[0.63–1.00], p = 0.013). ATI levels drawn at Doses 4 and 5 were all negative. IFX CL is variable and affected by factors including weight, ALB, disease activity and endoscopic severity. Under dosing is common in lower age bracket, due to higher drug CL/kg using current weight-based dosing. Paediatric IBD patients may benefit from precision medicine using PK model-based (dashboard) dose adjustments where individualised dosing can be calculated based on individual patient factors.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».