S37 Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients With Moderately to Severely Active Crohn’s Disease: U-ENDURE Phase 3 Results
Notice bibliographique
Résumé
Background: Efficacy and safety of upadacitinib (UPA) 15 mg (UPA15) once daily (QD) and UPA 30 mg QD (UPA30) maintenance therapy in patients with Crohn’s disease (CD) were evaluated in U-ENDURE. Methods: Patients with moderate to severe CD who responded (≥30% decrease average daily very soft/liquid stool frequency [SF] and/or average daily abdominal pain score [APS], neither greater than baseline) to 12-weeks (wks) of UPA 45 mg QD induction therapy were eligible for U-ENDURE. At wk0, patients were randomized (1:1:1) to receive UPA15, UPA30 or placebo (PBO) as maintenance therapy for 52 wks1. Co-primary endpoints, clinical remission per CD activity index (CDAI) or SF/APS and endoscopic response, were evaluated at wk52. Other efficacy and safety outcomes were evaluated at or through wk52. Results: At wk52, greater proportion of patients receiving UPA15 (n = 169) and UPA30 (n = 168) vs PBO (n = 165) achieved clinical remission per CDAI (37.3% [95%CI: 30.0%, 44.6%] and 47.6% [40.1%, 55.2%] vs 15.1% [9.6%, 20.6%]) and SF/APS (35.5% [28.3%, 42.7%] and 46.4% [38.9%,54.0%] vs 14.4% [9.0%,19.8%]) (all P < 0.0001 vs PBO for both doses). UPA15 and UPA30 patients attained greater rates of endoscopic response vs PBO (27.6% [95%CI: 20.8%, 34.4%] and 40.1% [32.7%, 47.6%] vs 7.3% [3.3%, 11.2%]; P < 0.0001 vs PBO for both doses). UPA15 and UPA30 were superior vs PBO for key secondary endpoints at wk52 including clinical response (41.4% and 51.2% vs 15.2%), endoscopic remission (19.1% and 28.6% vs 5.5%), maintenance of clinical remission (per CDAI: 49.5% and 65.2% vs 21.2%; per SF/APS: 50.5% and 60.0% vs 19.6%), corticosteroid-free clinical remission in all patients (per CDAI, 36.7% and 46.4% vs 14.5%; per SF/APS, 34.9% and 44.6% vs 14.4%) and in patients with baseline steroid use (per CDAI, 39.7% and 39.7% vs 4.9%; per SF/APS, 38.1% and 38.1% vs 4.9%), clinical+endoscopic remission (per CDAI, 14.8% and 23.2% vs 3.7%; per SF/APS, 13.7% and 22.6% vs 4.3%), and change from baseline in IBDQ total score (LS mean[SE]: 59.3[3.22] and 64.5[3.15] vs 46.4[4.02]) (all P < 0.01 vs PBO for both doses). UPA30-treated patients also demonstrated significant improvement from baseline in FACIT-F vs PBO (LS mean[SE]: 16.1[1.02] vs 12.0[1.34]; P < 0.001). Rates of adverse events (AE) and serious AEs were similar across UPA groups; AE leading to treatment discontinuation rates were similar across groups. Most common AE was CD worsening (UPA15: 29.7 events/100 patient-years [E/100PY], UPA30: 12.0E/100PY, PBO: 58.0E/100PY). Serious infection rates were similar across groups (6.1-8.4 E/100PY); herpes zoster rate was higher in UPA30 (7.2E/100PY) vs PBO (4.7E/100PY) and UPA15 (4.0E/100PY). Malignancies excluding non-melanoma skin cancer (NMSC) were reported in 1 UPA15 patient and 2 UPA30 patients; all events were diagnosed within 9 months of first UPA exposure. One gastrointestinal perforation was reported in each group. One event of hepatic vein thrombosis was reported in UPA30. No deaths, tuberculosis, NMSC, or adjudicated cardiovascular events occurred in any group. Conclusion(s): Among patients with moderate to severe active CD who respond to UPA induction therapy, UPA15 and UPA30 maintenance treatments were well tolerated and superior to PBO for all clinical and endoscopic outcomes, and most quality-of-life outcomes at wk52.
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 | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 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 ».