S714 52-Week Risankizumab Subcutaneous Maintenance Dosing Is Efficacious and Well Tolerated in Patients With Moderate to Severe Crohn’s Disease Who Had Delayed Response to 12-Weeks IV Risankizumab Induction
Notice bibliographique
Résumé
Introduction: In patients with moderate to severe Crohn's disease (CD), the ADVANCE and MOTIVATE phase 3 induction studies showed intravenous (IV) risankizumab (RZB), an anti-p19 interleukin-23 inhibitor, to be superior to placebo (PBO) for achieving clinical and endoscopic endpoints at Week (Wk) 12.1 Here, we evaluated the long-term efficacy and safety of RZB during the FORTIFY maintenance study in patients with delayed clinical response to IV RZB induction. Methods: Patients who did not achieve clinical response (defined as ≥30% decrease in average daily stool frequency [SF] and/or ≥30% decrease in average daily abdominal pain score [APS], both not worse than baseline of induction) following 12-wks IV RZB (600 mg or 1200 mg) induction dosing, but who did achieve clinical response at Wk 24 following an additional 12-wks RZB subcutaneous (SC) dosing (“delayed responders”) were examined. These patients continued on the same dose (RZB 180 mg SC [N = 30], RZB 360 mg SC [N = 33]) in the FORTIFY maintenance study and were analyzed for clinical and endoscopic improvements at Wk 52. Results: At FORTIFY Wk 52, most delayed responders achieved clinical remission and response with 180 mg or 360 mg RZB SC (Table, see footnotes for endpoint definitions). In addition, patients receiving RZB SC (180 mg or 360 mg) also achieved endoscopic response (36.7%, 45.5%), endoscopic remission (40.0%, 42.4%), deep remission (40.0%, 39.4%), ulcer free endoscopy (27.6%, 24.2%), and the combined endpoint of SF/APS clinical remission + endoscopic response (23.3%, 36.4%). Moreover, a dose-response trend was observed, with numerically higher response rates observed with RZB 360 mg SC relative to 180 mg SC for most outcomes, including clinical remission (CDAI and SF/APS), CDAI clinical response, enhanced clinical response, endoscopic response, endoscopic remission, and the composite endpoint of SF/APS clinical remission + endoscopic response. SC RZB maintenance dosing in delayed responders was well tolerated. The profile of treatment emergent adverse events was consistent with the known safety profile of patients with CD treated with RZB. No new safety risks were identified. Conclusion: RZB was efficacious in patients with delayed clinical response to RZB induction. These findings underscore the additional clinical benefit of SC RZB treatment in maintenance, even in patients who were initial non-responders to 12-wks IV RZB induction. RZB was well tolerated in delayed responders with no new safety risks identified. Table 1. - Efficacy and Safety after 52-Weeks Maintenance SC RZB Dosing in Delayed Responders (NRI-NCa) Responder GroupTreatment Group, n (%) [95% CI] CDAI Clinical Response Enhanced Clinical Response CDAI Clinical Remission SF/APS Clinical Remission Endoscopic Response Ulcer Free Endoscopy Endoscopic Remission SF/APS Clinical Remission and Endoscopic Response Deep Remission RZB 180 mg SC delayed responders, Wk 24 53.3(6/30)[35.5, 71.2] 56.7(17/30)[38.9, 74.4] 53.3(16/30)[35.5, 71.2] 43.3(13/30)[25.6, 61.1] 36.7(11/30)[19.4, 53.9] 27.6(8/29)[11.3, 43.9] 40.0(12/30)[22.5, 57.5] 23.3(7/30)[8.2, 38.5] 40.0(12/30)[22.5, 57.5] RZB 360 mg SC delayed responders, Wk 24 75.8(25/33)[61.1, 90.4] 66.7(22/33)[50.6, 82.8] 66.7(22/33)[50.6, 82.8] 54.5(18/33)[37.6, 71.5] 45.5(15/33)[28.5, 62.4] 24.2(8/33)[9.6, 38.9] 42.4(14/33)[25.6, 59.3] 36.4(12/33)[20.0, 52.8] 39.4(13/33)[22.7, 56.1] Responder GroupTreatment Group, (E/100PYs) Deaths Serious infections All treatment emergent adverse events AE related to COVID-19 Serious AE Hepatic events Injection site reactions AE leading to discontinuation of study drug Crohn's Disease RZB 180 mg SC (N=31) (PYs=27.5) delayed responders, Wk 24 0 0 132 (479.8) 0 6 (21.8) 0 6 (21.8) 2 (7.3) 7 (25.4) RZB 360 mg SC (N=33) (PYs=32.1) delayed responders, Wk 24 0 1 (3.1) 83 (258.9) 0 4 (12.5) 1 (3.1) 2 (6.2) 0 7 (21.8)
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».