A129 CYP2C19 PHARMACOGENETIC TESTING IN PAEDIATRIC PATIENTS WITH EOSINOPHILIC ESOPHAGITIS INFLUENCES DOSING OF PROTON-PUMP-INHIBITORS AND RESPONSE TO THERAPY
Notice bibliographique
Résumé
Abstract Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder that can be treated with a proton pump inhibitor (PPI). Pharmacogenetics (PGx) is the study of how variations in an individual’s genome influences drug response. Genetic variation in the metabolism gene CYP2C19 can produce differences in enzyme activity which is known to be a contributing factor for therapeutic failure with PPI treatment. Use of 2nd generation PPI (rabeprazole) can be beneficial in some as this PPI is less effected by CYP2C19 metabolism. PGx has been studied in PPI therapy for peptic ulcer disease but has not been demonstrated in patients with EoE. Aims To describe the CYP2C19 metabolism in patients with EoE on PPI and to estimate the clinical utility of PGx testing in directing subsequent changes in therapy with improvement in remission rates. Methods Interim analyses of a single centre, non-interventional, ongoing descriptive pilot study investigating CYP2C19 metabolism in patients with EoE, as part of a larger PGx pilot study and EoE- AHEAD Registry Study at SickKids. Patients with EoE that were newly diagnosed and started PPI or those not in remission on current non-PPI therapy or not in remission on dose PPI (2 mg/kg/day, max 30 mg lansoprazole BID) were included. Active disease was defined as a peak eosinophil count >15/hpf. Results 37 patients met the inclusion criteria with completed PGx test; mean age was 13 years, 29(78%) were male, and 13(35%) had concurrent atopic disease. PGx testing showed that 12(32%) and 4(11%) were rapid (RM) and ultrarapid metabolizers (URM) respectively (Fig.1), which is significantly higher than the population average. Of this subgroup, 9 started rabeprazole, 3 had a lansoprazole dose increase, and 4 had no changes. Overall, changes in therapy based on PGx testing were made in 29(78%) patients, 8 are awaiting follow-up (Fig 2). Currently, the patients with available repeat biopsy results after PGx test-guided therapy changes is limited due COVID-19 related delays in endoscopies. Conclusions The preliminary findings of our study using PGx to guide PPI dosing in pediatric patients with EoE demonstrate that PGx test results lead to a change in clinical management in most patients. In RM and URM, PGx results trigger an adjustment of PPI dose or type could lead to earlier disease remission in PPI-responsive patients, thereby optimizing PPI efficacy. PGx may support dose reduction in poor metabolizers aiming to avoid long-term adverse events. Further correlation with endoscopy and histology findings of patients after PGx-guided therapy changes will follow. Furthermore, it is important to examine if CYP2C19 variant information available before PPI therapy further streamlines an initial phase of the treatment. Funding Agencies Dr. Marcon: J Garfield Campbell Fund, Dr. Hulst: Start-up Funds from the Department of Pediatrics at SickKids
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) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| 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) | 0,002 | 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 ».