P789 Impact of risk factors for Janus kinase inhibitor use identified by the Pharmacovigilance Risk Assessment Committee on the safety and efficacy of ozanimod in patients with moderately to severely active ulcerative colitis
Notice bibliographique
Résumé
Abstract Background With the emergence of oral small molecule therapies for ulcerative colitis (UC), there is a need for identification of favourable safety and efficacy profiles for these therapies. The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency reassessed the benefit–risk of Janus kinase inhibitor (JAKi) use based upon data showing increased risk of major adverse cardiovascular (CV) events (MACE) and cancer with tofacitinib. Accordingly, the PRAC identified criteria for which a JAKi should be used only if no alternatives are available or used with caution. This analysis of the phase 3 True North (TN) study (NCT02435992) evaluated the safety and efficacy of ozanimod (OZA) by the presence of JAKi PRAC criteria in patients with moderately to severely active UC. Methods Analyses were performed in TN patients comparing those with ≥1 vs no JAKi PRAC criteria at TN baseline (BL). The criteria included age ≥65 y, history of major CV problems, history of CV risk factors (eg, hypertension, high-density lipoprotein cholesterol <40 mg/dl, diabetes mellitus), current or former smoker, and history of cancer. Safety was monitored through Week (W) 52 and efficacy endpoints were assessed at W10 and W52 in patients receiving OZA or placebo (PBO). Results At TN BL, 491 patients had ≥1 JAKi PRAC criteria and 521 had no JAKi PRAC criteria. BL patient characteristics were generally similar across groups, but the ≥1 JAKi PRAC criteria group was older (46-48 y vs 36-37 y), with more male patients (62-72% vs 52-61%) and longer UC disease duration (7-9 y vs 6-7 y) vs the no JAKi PRAC criteria group. Treatment-emergent adverse events (TEAEs) occurring during the induction and maintenance periods are shown in Table 1. Overall, TEAE rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; however, rates of serious TEAEs and TEAEs leading to treatment discontinuation were similar. Bradycardia and hypertension rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; rates of other CV and thromboembolic events and cancer were similar between groups. At W10, OZA was more effective than PBO for clinical remission and response, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1A). At W52, more OZA/OZA pts achieved all endpoints vs OZA/PBO pts, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1B). Conclusion In patients with UC, JAKi PRAC criteria were not associated with greater rates of MACE or cancer with OZA for up to 52 wk, nor did they affect OZA efficacy, suggesting that OZA is a safe and tolerable oral small molecule treatment option for such patients.
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 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 | 0,000 |
| 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 | 0,000 | 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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, 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 ».