215 Efficacy and Safety of Upadacitinib as an Induction Therapy for Patients With Moderately-to-Severely Active Ulcerative Colitis: Combined Results From 382 Subjects in the Phase 2b Study U-ACHIEVE
Notice bibliographique
Résumé
INTRODUCTION: We assessed efficacy/safety of upadacitinib (UPA) in a ph 2b induction study (part 1) in pts with moderately-to-severely active ulcerative colitis (UC). Additional Pts were enrolled in part 2. We present the efficacy and safety of the combined results of part 1 and part 2 METHODS: Adults with moderately-to-severely active UC (Adapted Mayo Score 5–9 points and centrally-read endoscopy subscore 2–3) were randomised 1:1:1:1:1 to receive extended-release UPA7.5, 15, 30, 45 mg once daily (QD) or placebo for 8 wks (N = 250). In part 2, 132 pts were randomised to UPA30 or 45 mg QD with 1:1 allocation for 8 weeks. Pairwise comparisons between UPA and PBO for primary endpoint of clinical remission per Adapted Mayo Score at Week 8 (defined as stool frequency subscore ≤1, rectal bleeding subscore = 0, and endoscopic subscore ≤1) and ranked secondary endpoints were conducted using Cochran-Mantel-Haenszel test stratified by previous biologic use, BL corticosteroid use, and BL Adapted Mayo score. No multiplicity adjustments were applied. Non-responder imputation was used for missing values in 13% of pts. Treatment emergent adverse events (AEs) were reported from first dose of study drug to up to 30 days after last dose. RESULTS: A total 382 pts were randomised with mean (SD) age of 42.7 (14.3) yrs and disease duration of 8.4 (7.4) yrs. Primary endpoint of clinical remission, and secondary endpoints of endoscopic improvement, clinical response per Adapted Mayo score, clinical response per Partial Mayo score, endoscopic remission, and histologic improvement were significantly higher with UPA doses ≥30 mg QD vs PBO (Table 1). Incidences of AEs were similar across UPA groups and numerically higher in PBO group. Rates of serious AEs were 10.9%, 0%, 4.1%, 4.3% and 4.9% for PBO and UPA 7.5, 15, 30, and 45 mg QD, respectively. Serious infections occurred in pts receiving PBO (4.3%, n = 2), 15 mg QD (2.0%, n = 1), 30 mg QD (0.9%, n = 1), and 45 mg QD (1.6%, n = 2). One case of herpes zoster and pulmonary embolism (PE)/deep vein thrombosis (DVT) with UPA 45 mg QD were reported. PE/DVT was reported 26 days after study drug discontinuation due to UC worsening and hospitalization. No deaths were reported. CONCLUSION: In this combined analysis, primary and ranked secondary endpoints consistently met statistical significance with UPA doses ≥ 30 mg QD vs PBO in pts with moderately-to-severely active UC. These results are consistent with part 1 intention-to-treat analysis. 1,2 UPA was well-tolerated and no new safety signals were identified.
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 | 0,003 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 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 | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».