DOP002 Efficacy and safety of upadacitinib after 4 years of treatment in patients with moderately to severely active ulcerative colitis: interim long-term data from the phase 3 open-label extension study (U-ACTIVATE)
Notice bibliographique
Résumé
Abstract Background Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC),1,2 has shown sustained efficacy and an acceptable safety profile in long-term studies of immune-mediated diseases.3,4 Methods We report efficacy and safety of UPA from the U-ACTIVATE (NCT03006068) long-term extension (LTE). Patients (pts) had approximately 4 years (yrs) of maintenance therapy, consisting of 1-yr U-ACHIEVE maintenance and 3 yrs LTE. Pts were randomised to placebo (PBO) or UPA 45 mg once daily (QD) for the 8-week (wk) induction. Clinical responders were re-randomised to PBO, UPA 15 mg QD (UPA15), or UPA 30 mg QD (UPA30) for the 52-wk maintenance. Pts in clinical remission (CR) per Adapted Mayo score (AMS) at wk 52 of the maintenance study continued their double-blind treatment upon entering the LTE. Non-remitters originally randomised to UPA15 were eligible to escalate to UPA30, those randomised to blinded UPA30 continued on blinded UPA30, and those assigned to PBO were eligible to escalate to UPA15 in a blinded manner; see footnote for additional information (Table 1). The study was not designed to compare UPA15 and UPA30 doses. Efficacy was evaluated by CR (per AMS and Partial Mayo score), maintenance of CR per AMS, endoscopic improvement (EI), maintenance of EI, endoscopic remission (ER), and maintenance of ER during the LTE at wk 144. Efficacy data are presented as observed (AO), as well as modified non-responder imputation (mNRI). Treatment-emergent adverse events (TEAEs) were presented as exposure-adjusted event rates (EAERs; events per 100 pt yrs [E/100 PY]); cut-off date: June 30, 2024. Results At LTE wk 144, improvements in CR per AMS and maintenance of CR per AMS were observed in more than half of pts treated with UPA15 or UPA30 (Table 1). ER was achieved by nearly half of pts and more than half of pts maintained ER at LTE wk 144 with UPA15 and UPA30. For safety, 369 pts (UPA15, N=142; UPA30, N=227) with 1043.5 PY (UPA15, 397.4 PY; UPA30, 646.1 PY) of exposure to UPA were analysed (Table 2). Rates of serious TEAEs and TEAEs leading to treatment discontinuation were similar across treatment groups. There was 1 TEAE leading to death (EAER: 0.2 E/100 PY) in a pt requiring prolonged hospitalisation for worsening COVID-19 infection in the UPA30 group. Conclusion Pts achieved and maintained key clinical and endoscopic outcomes through 4 yrs of UPA treatment. Response rates based on mNRI were consistent with the AO approach, supporting the long-term efficacy of UPA. The long-term safety profile for UPA in pts with UC was consistent with previous analyses,1,2 with no new safety risks identified in the ongoing LTE study. These analyses continue to support the favourable benefit–risk in pts with UC. References 1. Danese S, et al. Lancet 2022;399:2113–28 2. Vermeire S, et al. Lancet Gastroenterol Hepatol 2023;8:976–89 3. Fleischmann R, et al. RMD Open 2022;8:e002012 4. Simpson EL, et al. JAMA Dermatol 2022;158:404–13
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 | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».