A112 EARLY USE OF THERAPEUTIC DRUG MONITORING TO INDIVIDUALIZE INFLIXIMAB THERAPY IN PAEDIATRIC IBD: A MULTICENTRE PROSPECTIVE COHORT STUDY
Pourquoi ce travail est dans la base
Une base qui oublie comment elle a trouvé un travail ne peut pas être vérifiée. Voici les voies qui ont admis celui-ci.
Notice bibliographique
Résumé
Utilization of therapeutic drug monitoring (TDM) to individualize biologic therapy is a logical strategy, given the variable drug clearance and multiple factors influencing pharmacokinetics. Indeed, previously documented wide variability of infliximab levels have been observed early post induction in pediatric patients. However, a randomized controlled trial in adults did not demonstrate improved outcomes with TDM implemented following induction phase of infliximab treatment. The aim of the study was to determine infliximab trough levels during induction therapy in children with IBD, with the goal to pre-emptively personalize maintenance dosing. Beginning in May 2016, children with IBD at participating sites in the Canadian Children IBD Network, when prescribed 3-dose infliximab induction therapy via either standard or intensified regimen, had pre-infusion trough levels measured by ELISA at the time of 3rd dose. An algorithm incorporating this trough level and the interval between doses 2 and 3 was used to determine timing and dose of first maintenance infusion, aiming to provide a trough level of 5–10 ug/mL when tested before dose 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 clinical disease activity (physician global assessment and wPCDAI or PUCAI) on early trough levels were assessed. From May to October 2016 at 6 participating sites, 77 children (mean age 12.4 years, 57% male, 53% CD, 47% UC/IBD-U) received 3-dose infliximab induction. CD patients were infused in standard fashion at weeks 0, 2, 6 with a mean dose of 5.5mg/kg/dose and concomitant immunomodulation (93% methotrexate; 7 % azathioprine); median pre-dose 3 IFX level was 11.9ug/ml (IQR: 8.5–27.2). UC/IBD-U patients (18% steroid-dependent, 82% steroid-refractory) received more drug (mean 6.8mg/kg/dose across 3 doses) and via an intensified regimen in 34%. Pre-dose 3 IFX levels (median 13.5ug/ml;IQR: 4.9–24.3) were comparable to CD despite higher dosing. 25% of UC/IBD-U patients vs. 11% of CD patients had infliximab trough level <5 ug/ml at time of dose 3. Variability in infliximab exposure is evident during induction. Patients with UC cleared drug more rapidly, requiring higher weight-based dosing and a more intensive regimen to achieve comparable drug levels post induction. Ongoing monitoring of trough levels measured prior to dose 4 in this cohort will determine whether early TDM with personalized dosing more consistently ensures adequate drug exposure with subsequent better clinical outcome. None
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.
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 découle