S0652 Real World Exposure-Response Relationship of Vedolizumab in Inflammatory Bowel Disease: A Pooled Multicenter Observational Cohort Analysis of Clinical and Modeled Pharmacological Data
Notice bibliographique
Résumé
INTRODUCTION: The role of vedolizumab (VDZ) therapeutic drug monitoring in patients with ulcerative colitis (UC) or Crohn's disease (CD) is under investigation. However, a thorough understanding of the relationship between VDZ serum concentrations and clinical outcomes is lacking. METHODS: ERELATE was a retrospective cohort study conducted at 9 centers in 6 countries. Data were pooled from real-world clinical cohorts of patients with UC or CD treated with VDZ. Clinically important treatment outcomes based on definitions commonly used across centers were collected at Weeks 14, 26, and 52. Using a population pharmacokinetic model,1 VDZ dosing, baseline body weight, and albumin concentration were used to predict VDZ concentrations. A Bayesian approach incorporated observed VDZ concentrations to refine individual predicted concentrations. Relationships between predicted concentrations and observed clinically important outcomes were investigated. VDZ concentration thresholds were determined using the optimal Youden index point along the receiver operating characteristic curve. Correlation and agreement between observed and predicted concentrations were evaluated using Spearman (ρ) and intra-class correlation (ICC) coefficients, respectively. RESULTS: In total 695 patients (304 UC, 391 CD) were included; 47.9% were male. Median age was 39 years, median disease duration was 9 years, and 86.3% had prior anti-tumor necrosis factor exposure. Clinically important outcome rates for UC and CD are shown in Table 1. Significant correlation ([ρ = 0.879; P < 0.01] across all timepoints) and agreement (ICC = 0.722; P < 0.01) were noted between observed and predicted concentrations, indicating adequate Bayesian model prediction of individual VDZ concentrations. Observed exposure-response relationships were more pronounced in UC than CD. Differences in VDZ concentration and drug concentration area under the curve from Weeks 0–6 were observed between remitters and non-remitters for UC and CD combined (Table 2). Predicted VDZ concentrations of 30.8 and 33.8 µg/mL at Week 6 and 16.6 and 14.4 µg/mL at Week 14 were associated with clinical remission and deep remission, respectively, at Week 52. CONCLUSION: These real-world data confirm GEMINI trial findings of significant relationships between VDZ serum concentration and clinical outcomes. Adequate drug concentrations during induction therapy may be important predictors of short- and long-term treatment outcomes.Table 1.: Clinically Important Outcomes in Patients With UC or CDTable 2.: Predicted Vedolizumab Trough Concentrations Associated With Clinical and Deep Remission in Patients With UC or CD
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 | 0,017 | 0,015 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,003 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».