S733 Impact of Inflammatory Burden on Efficacy of Upadacitinib Maintenance Therapy in Ulcerative Colitis: Results From the Phase 3 U-ACHIEVE Study
Notice bibliographique
Résumé
Introduction: Upadacitinib (UPA) has demonstrated superior efficacy to placebo (PBO) and a favorable safety profile in patients with moderately to severely active ulcerative colitis (UC) in trial U-ACHIEVE Maintenance, in which two maintenance doses of UPA (30mg and 15mg once daily [QD]) were evaluated.1–3 However, data are limited on the impact of inflammatory burden on the efficacy of the two maintenance doses. Methods: The primary efficacy analysis of U-ACHIEVE Maintenance included the first 451 patients who achieved a clinical response (per Adapted Mayo score) after 8 weeks of UPA 45mg QD treatment in the induction trials. The primary endpoint was clinical remission per Adapted Mayo score at Week 52 and a key secondary endpoint was endoscopic improvement at Week 52. This post hoc analysis evaluated the efficacy, based on these endpoints, of UPA 30mg vs UPA 15mg maintenance therapy in patients in U-ACHIEVE Maintenance stratified by three measures of inflammatory burden: baseline Full Mayo score >9 vs ≤9, presence of pancolitis (yes vs no), and presence of ≥1 extraintestinal manifestation (yes vs no). Results: Overall, 451 patients (PBO: n=149, UPA 15mg: n=148, and UPA 30mg: n=154) were included in the intent-to-treat maintenance population. Both UPA 30mg and UPA 15mg demonstrated favorable efficacy compared with PBO, regardless of the inflammatory burden (Table). However, the differences in proportions of responders who achieved clinical remission at Week 52 and who received UPA 30mg vs UPA 15mg were greater in patients with a high inflammatory burden (difference range: 12.0–22.0%) than those patients without a high inflammatory burden (difference range: 1.4–6.2%; Table). Similar results were seen for proportions of patients who achieved endoscopic improvement at Week 52 (high inflammatory burden [difference range: 12.0–26.1%] relative to those without high inflammatory burden [difference range: 0.2–14.1%]). Conclusion: Both UPA maintenance doses were efficacious compared with PBO, regardless of inflammatory burden, in the achievement of clinical remission and endoscopic improvement. Although results should be interpreted with respect to the small sample size in some subgroups and the post hoc nature of the analysis, these data suggest that patients with a high inflammatory burden of UC may have a relatively greater benefit from UPA 30mg than UPA 15mg, compared with those without high inflammatory burden. Table 1. - PBO, n/N (%)(N=149) UPA 15 mg QD, n/N (%)(N=148) UPA 30 mg QD, n/N (%)(N=154) Difference between UPA 30 mg vs UPA 15 mg a , % Primary endpoint: Clinical remission b at Week 52 per Adapted Mayo Score BL Full Mayo score ≤9 BL Full Mayo score >9 7/74 (9.5)11/75 (14.8) 40/75 (53.1)23/73 (31.2) 40/73 (54.5)40/79 (50.4) 1.419.2 Pancolitis at BL, noPancolitis at BL, yes 13/79 (16.5)5/70 (7.1) 31/66 (46.6)32/82 (38.8) 36/68 (52.8)44/86 (50.8) 6.212.0 EIM at BL, noEIM at BL, yes 13/112 (11.6)5/37 (13.7) 50/112 (44.3)13/36 (36.1) 56/113 (49.4)24/41 (58.1) 5.122.0 Key secondary endpoint: Endoscopic improvement c at Week 52 BL Full Mayo score ≤9BL Full Mayo score >9 8/74 (10.8)14/75 (18.1) 45/75 (60.4)27/73 (36.7) 44/73 (60.6)50/79 (62.8) 0.226.1 Pancolitis at BL, noPancolitis at BL, yes 16/79 (20.3)6/70 (8.0) 33/66 (49.6)39/82 (47.9) 43/68 (63.7)52/86 (59.9) 14.112.0 EIM at BL, noEIM at BL, yes 15/112 (13.7)6/37 (16.9) 57/112 (50.9)15/36 (41.7) 68/113 (60.2)27/41 (65.4) 9.323.7 Data are from the ITT population, defined as the first 450 randomized and treated patients with 8-week UPA 45 mg QD induction treatment who were enrolled in Cohort 1 under the protocol for the 52-week maintenance treatment period. The actual number of patients in the analysis was 451 due to the same enrollment date of the 450th and 451st patients. Non-responder imputation incorporating multiple imputations was performed to handle missing data due to COVID-19 incidence.aNot part of the predefined statistical analyses.bAdapted Mayo score ≤2, with stool frequency subscore ≤1 (and not greater than induction baseline), rectal bleeding subscore of 0, and endoscopic subscore ≤1.cEndoscopic subscore ≤1.BL, baseline; EIM, extraintestinal manifestation; ITT, intent-to-treat; PBO, placebo; QD, once daily; UPA, upadacitinib.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 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 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».