S4 Risankizumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomized Phase 3 INSPIRE Study
Notice bibliographique
Résumé
Background: Risankizumab (RZB), a monoclonal antibody neutralizing interleukin (IL)-23p19, was evaluated for efficacy and safety of induction therapy in patients with moderately to severely active ulcerative colitis (UC) in the phase 3 trial, INSPIRE (NCT03398148). Methods: Eligible patients (18-80 years) with moderately to severely active UC (Adapted Mayo score of 5 – 9 points) and an endoscopic subscore of 2-3 (per central review) were enrolled. Patients were required to have demonstrated intolerance or inadequate response to conventional and/or advanced therapies (biologics, JAK inhibitors, and S1P receptor modulators). Patients (N=975) were randomized 2:1 to receive either RZB 1200 mg intravenously or placebo (PBO) at Weeks 0, 4, and 8, stratified by baseline corticosteroid use (yes vs no), baseline adapted Mayo Score (≤ 7 vs > 7), and number of advanced therapy failures (0, 1, >1). The primary endpoint was clinical remission (per Adapted Mayo Score defined as stool frequency subscore ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1 without friability) at Week 12. Key, ranked secondary endpoints included clinical response, endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR) at Week 12, unless otherwise noted. Results: Baseline characteristics were similar between treatment groups. A significantly greater proportion of patients receiving RZB (n=650) vs. PBO (n=325) achieved clinical remission (20.3% vs. 6.2%, adjusted treatment difference 14.0% [95% CI, 10.0%-18.0%], p < .00001). A greater proportion of patients achieved clinical remission for RZB vs. PBO in the advanced therapy-naïve (29.7% [n=317] vs. 8.4% [n=155], adjusted treatment difference 21.3% [95% CI, 14.6%-27.9%]) and advanced therapy-IR (11.4% [n=333] vs. 4.3% [n=170], adjusted treatment difference 7.2% [95% CI, 2.6%-11.8%]) subpopulations. All ranked secondary endpoints were met. Significantly higher clinical response rates (per Adapted Mayo Score at week 12: 64.3% vs. 35.7%, adjusted treatment difference 28.6% [95% CI, 22.3%-34.8%]; per partial Adapted Mayo Score at Week 4: 52.2% vs. 30.5%, adjusted treatment difference 21.8% [95% CI, 15.6%-28.1%]), endoscopic improvement (36.5% vs. 12.1%, adjusted treatment difference 24.3% [95% CI, 19.3%-29.4%]), endoscopic remission (10.6% vs. 3.4%, adjusted treatment difference 7.2% [95% CI, 4.2%-10.2%]), HEMI (24.5% vs. 7.7%, adjusted treatment difference 16.6% [95% CI, 12.3%-21.0%]), and HEMR (6.3% vs. 0.6%, adjusted treatment difference 5.6% [95% CI, 3.5%-7.7%]) were met for RZB vs. PBO, respectively (p < .00001 for all endpoints). Adverse event (AE) rates were 42.1% in RZB vs 49.7% in PBO, serious AEs (2.3% vs 10.2%), severe AEs (2.5% vs 10.2%), AEs leading to discontinuation of study drug (0.6% vs 3.7%), and serious infections (0.6% vs 1.2%), all numerically lower in the RZB arm. No adjudicated major adverse cardiovascular events, adjudicated anaphylaxis, or serious hepatic events reported. One death occurred in the RZB group due to covid-19 pneumonia, with no possibility of being related to study drug according to the investigator. Conclusions: RZB was superior to PBO as an induction therapy in patients with moderately to severely active UC for clinical remission and all secondary clinical, endoscopic, and endoscopic-histologic endpoints. RZB was well-tolerated, and no new safety risks were observed.
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 | 0,004 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| 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) | 0,005 | 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 ».