S845 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
Introduction: 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 a large 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 a diagnosis of UC for at least 3 months prior to baseline, and 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 (IV) or placebo (PBO) at Weeks (Wks) 0, 4, and 8. The primary endpoint was clinical remission (per Adapted Mayo score) at Wk 12 (see Figure 1 legend for definitions). Key, ranked secondary endpoints included clinical response, endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement (HEMI), and histologic-endoscopic mucosal remission (HEMR), which were measured at Wk 12, unless otherwise noted. Results: Baseline characteristics were similar between treatment groups. Significantly more patients receiving RZB achieved clinical remission vs PBO (20.3% vs 6.2%, adjusted treatment difference 14.0% [95% CI, 10.0%-18.0%], P< .00001, Figure 1A). All ranked secondary endpoints were met. RZB attained higher rates of clinical response (per Adapted Mayo score at Wk 12 and per Partial Adapted Mayo score at Wk 4), endoscopic improvement, endoscopic remission, HEMI, and HEMR, compared to PBO (P< .00001 for all endpoints, Figure 1B). Adverse event (AE) rates were 42.1% in RZB vs 49.7% 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%) were numerically lower in the RZB arm. No adjudicated major adverse cardiovascular events, adjudicated anaphylaxis, or serious hepatic events were reported. One death occurred in the RZB group due to COVID-19 pneumonia. Conclusion: In patients with moderately to severely active UC, RZB was superior to PBO as an induction therapy for clinical remission and all secondary clinical, endoscopic, and endoscopic-histologic endpoints. RZB was well-tolerated, and no new safety risks were observed.Figure 1.: Primary and Key Secondary Endpoints All patients in this dataset were included here within the ITT population. Endpoints were assessed at Week 12 unless otherwise noted. Clinical Remission per Adapted Mayo score: Stool frequency subscore ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1 without friability Clinical Response per Adapted Mayo: Decrease from baseline ≥ 2 points and ≥ 30%, in addition to a decrease in RBS ≥ 1 or an absolute rectal bleeding score (RBS) ≤ 1 Clinical Response per Partial Adapted Mayo: Decrease from baseline ≥ 1 point and ≥ 30% a decrease in RBS ≥ 1 or an absolute RBS ≤ 1 Endoscopic Improvement: Endoscopic subscore of 0 or 1 without friability Endoscopic Remission: Endoscopic subscore = 0 Histologic-Endoscopic Mucosal Improvement (HEMI): Endoscopic subscore of 0 or 1 without friability and Geboes score ≤ 3.1 Histologic-Endoscopic Mucosal Remission (HEMR): Endoscopic subscore of 0 and Geboes score < 2.0 Results were stratified by baseline corticosteroid use (yes vs no), baseline Adapted Mayo score (≤ 7 vs > 7), and the number of advanced therapy failures (0, 1, >1). Results are based on non-responder imputation incorporating multiple imputation (NRI-MI) to handle missing data due to COVID-19 or due to geopolitical conflict in Ukraine or surrounding areas. ***P-value <.00001 vs PBO. P-value for treatment difference between RZB 1200 mg IV and PBO, using Cochran-MantelHaenszel (CMH) test for categorical endpoints, controlling for stratification factors. IR, inadequate response.
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 | 0,002 |
| 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) | 0,004 | 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 ».