P565 Real-world use of azathioprine metabolites changes clinical management of inflammatory bowel disease
Notice bibliographique
Résumé
With ongoing sub-optimal efficacy of current therapies in achieving intestinal healing in IBD, the thiopurines, 6-mercaptopurine (6MP) and azathioprine (AZA), continue to have a role in IBD treatment. However, their complex metabolism results in inter-individual differences in clinical efficacy and risk of drug toxicity, making conventional weight-based dosing both inaccurate and potentially unsafe. Therapeutic drug monitoring (TDM) of thiopurine metabolites improves clinical outcomes through optimisation of dosing and monitoring for toxicity (Haines et al., 2011). Despite evidence for thiopurine TDM, there remain significant disparities in use, due in part to test availability. We recently described implementation of a novel thiopurine metabolite assay (Yang et al. poster, AACC, 2017). This study aims to determine the impact of thiopurine metabolite levels on physician decision-making and clinical management. Patients who had undergone thiopurine TDM as part of their outpatient care were identified and prospective and retrospective chart reviews performed to measure the impact of TDM on clinical management. Additional data were gathered from patient charts including demographics, dosing, clinical disease activity, concurrent medication use, and frequency of adverse effects. A second physician reviewed clinical scenarios with blinding of TDM results and original clinical management, and provided an opinion on clinical decision-making before and after unblinding of TDM results. A total of 92 IBD patients (63% CD, 37% UC) with available metabolite levels were included, of which 64% had active disease, and 43% were on combination therapy with a biologic. Levels of the active metabolite 6TG were sub-therapeutic in 52%, therapeutic in 29% and supra-therapeutic in 14%. High 6MMP: 6TG ratios were found in 26% of patients. Weight-based AZA doses accounted for only 5% of the variation in 6TG levels (r2 = 0.057, p = 0.02). TDM resulted in a change in clinical management in 64% of the cases. In 44% of those dosing was decreased, 19% dosing increased, and in 8% AZA discontinued. Allopurinol was added to the drug regimen in 12%. TDM also informed biologic management, with the addition of a biologic in 24%, optimisation of biologic in 7%, and change of biologic in 5%. Adverse reactions were observed in 28% of patients after weight-based dosing alone. The use of thiopurine TDM results informed IBD clinical decision-making in over two-thirds of patients. Additionally, therapeutic 6TG levels were seen in only 29% of patients. The demonstrated poor efficacy of weight-based dosing and significant impact of metabolite levels on clinical management highlights the need for greater availability and uptake of thiopurine TDM.
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 | 0,007 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 ».