Effects of Mirikizumab Versus Placebo on Histologic Inflammation Evaluated by Comprehensive Assessment in 5 Intestinal Segments in a Randomized Controlled Phase 3 Trial of Participants with Crohn’s Disease
Notice bibliographique
Résumé
Introduction Introduction: Mirikizumab (MIRI) increased histologic response (H-Res) and remission (H-Rem) relative to placebo (PBO) in the Phase 2 SERENITY trial. Material and Methods Methods: We compared the effect of MIRI on H-Res and H-Rem at week (W)12 and W52 to PBO by composite endpoints of response (clinical response by Patient-Reported Outcome [PRO] at W12 and W52 H-Res) and of remission (clinical response by PRO at W12 and W52 H-Rem) at W52. The overall population of patients with moderately-to-severely active Crohn’s Disease (CD), including those without prior biologic failure (non-BF), and those with prior BF were assessed, using data from the Phase 3 VIVID-1 trial (NCT03926130). Two biopsy specimens from each of the five intestinal segments (one ileal and four colonic) were obtained from the edge of ulcers, or the most inflamed mucosa from randomized patients at screening, W12, and W52. Clinical response by PRO was defined as≥30% decrease in stool frequency and/or abdominal pain with neither score worse than baseline. Results Results: At W12, treatment with MIRI resulted in nominally statistically significantly higher rates of H-Res in all three patient groups analyzed (p<.001) ([ Table 1 ]). At W12, differences between MIRI vs PBO were nominally significant in achieving H-Rem in all patients (p<.01) and in non-BF and BF patients (both p<.05). For W52 composite H-Res, differences between MIRI vs PBO were nominally statistically significant in all patient groups examined (p<.001). For W52 composite H-Rem, nominally statistically significant differences between MIRI vs PBO were observed in all patients (p<.001), in non-BF patients (p<.05), and in BF patients (p<.001). Table 1 Effects of Mirikizumab Versus Placebo on Histologic Inflammation Evaluated by Comprehensive Assessment in 5 Intestinal Segments in a Randomized Controlled Phase 3 Trial of Participants with Crohn’s Disease All patients Without Prior Biologic failure With Prior Biologic Failure PBO (N=199) MIRI (N=579) Difference (95% CI) PBO (N=91) MIRI (N=273) Difference (95% CI) PBO (N=88) MIRI (N=255) Difference (95% CI) W12 H-Res 30.7 52.7 22.2 (14.6-29.7)*** 37.4 58.6 21.2 (9.7-32.8)*** 22.7 47.8 25.1 (14.4-35.8)*** W12 H-Rem 12.1 22.1 10.2 (4.7-15.7)** 14.3 27.5 13.2 (4.3-22.1)* 4.5 12.2 7.6 (1.7-13.5)* W52 Composite H-Res 16.1 44.4 28.2 (21.6-34.7)*** 26.4 46.5 20.1 (9.3-31.0)*** 6.8 45.9 39.1 (31.0-47.1)*** W52 Composite H-Rem 8.5 23.3 14.7 (9.5-19.9)*** 14.3 24.9 10.6 (1.8-19.5)* 2.3 21.6 19.3 (13.4-25.2)*** Data are%;*p<.05;**p<.01;***p<.001 vs PBO “Without prior biologic failure“ and “With prior biologic failure“ were subgroups of all patients with active histologic disease at baseline. P-values for “All patients” were from the Cochran–Mantel–Haenszel test adjusting for baseline covariates. P-values for the “Without prior biologic failure“ and “With prior biologic failure“ subgroups were from the Fisher's exact test. H-Res=absence of epithelial neutrophils and epithelial damage, erosions, and ulceration or≥50% decrease in either the sum of the 5 segments of Robarts Histopathology Index or the Global Histologic Disease Activity Score. H-Rem=complete absence of mucosal neutrophils (in epithelium and lamina propria), and no epithelial damage, erosions, and ulcers. CI=confidence interval; H=histologic; MIRI=mirikizumab; PBO=placebo; Rem=remission; Res=response; W=week Conclusion Conclusions: Based upon strict definitions that applied to all 5 intestinal segments, MIRI achieved nominally significantly higher rates of H-Res and H-Rem compared to PBO in all patients at W12 and W52. The statistical difference was more pronounced in the BF population after one year of treatment. Publication History Article published online: 13 May 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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 | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,003 |
| 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 ».