P-012 YI Decisions to Dose Optimize Infliximab Using Pre-adjustment Therapeutic Drug Monitoring Result in Higher Trough Concentrations and Improved Endoscopic Outcomes
Notice bibliographique
Résumé
Increasingly, adequate infliximab (IFX) dosing is associated with improved outcomes in inflammatory bowel disease (IBD). Individualized therapeutic drug monitoring (TDM) to guide dose adjustment is cost-effective may offer clinical improvement. However, the effect of TDM-guided dose escalation on subsequent endoscopic outcomes remains unclear. We retrospectively evaluated the impact of TDM-driven dose adjustment on endoscopic remission. Data from primary responders to IFX who underwent dose escalation between 2008 and 2014 (interval reduction, dose increase or both) were reviewed. Patients with documented active endoscopic disease (ileal or colonic) <3 months prior to dose adjustment were included. 2 cohorts were examined: those with TDM-based decision to escalate and those with empiric decision. Outcomes recorded at median 6 months post- adjustment included endoscopic remission (Mayo <1, SES-CD <3), CRP, clinical remission and IBD-specific healthcare utilization (emergency visits, hospitalizations, steroid use, flares). TDM was performed using a homogenous mobility shift assay. Post-adjustment IFX and ATI concentration most discriminant for endoscopic remission were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission. Three hundred twelve dose optimization events were examined (149 TDM –based decision, 163 empiric). Patient demographics were not significantly different between groups apart from CRP ([mean ± SE] TDM: 23 ± 1.2; non-TDM: 11 ± 0.8 mg/L, P < 0.01). 63% of TDM group attained endoscopic remission compared to 48% non-TDM group (P < 0.05). 69% of the TDM group had significant clinical response compared to 57% non-TDM (P < 0.01) and also had fewer hospitalizations including ED visits (22% TDM versus 35% non-TDM group, P = 0.025). UC patients had a shorter time to optimization from first infusion (10 versus 20 months, P < 0.0001) and in the TDM group, had higher rates of endoscopic healing (64% compared to 46% CD) though this was not statistically significant. Median IFX trough levels increased significantly after TDM- based adjustment (from 1.5(pre) to 11 μg/mL (post); P < 0.0001) and were significantly higher than post-adjustment levels available in the empiric cohort (6.5 μg/mL, P = 0.015). Post-adjustment infliximab concentration of >4.5 μg/mL (area under the curve (AUC) = 0.8; 95% CI 0.71 to 0.88) and ATI concentration of <2.3 U/mL (AUC = 0.70; 95% CI 0.63 to 0.81) were associated with endoscopic remission. Multivariable analysis showed that IFX concentration (OR 1.2; [95% CI 1.1–1.3]; P < 0.0001) remained an independent predictor of endoscopic remission. TDM -guided dose adjustment is associated with higher post-adjustment trough levels, fewer ATI and in turn, higher endoscopic remission rates and fewer relapses.
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 | 0,001 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| 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) | 0,016 | 0,002 |
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 ».