S1452 Early Symptomatic Improvement With Mirikizumab Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From the Phase 3 VIVID-1 Study
Notice bibliographique
Résumé
Introduction: Mirikizumab (miri), an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical, endoscopic, and inflammatory biomarker endpoints, and an acceptable safety profile for patients (pts) with Crohn’s disease (CD) in the Phase 3 VIVID-1 study. We investigated the onset of symptomatic improvement and safety of miri as induction therapy through Week 12 (W12) for pts with CD. Methods: In VIVID-1, 1065 pts had moderately to severely active CD (unweighted daily average stool frequency (SF) ≥4 [loose and watery stools defined as Bristol Stool Scale Category 6 or 7] AND/OR unweighted daily average abdominal pain (AP) ≥2 at baseline) and prior failure to biologic and/or conventional therapy. Pts were randomized in a 6:3:2 ratio to receive miri (single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300mg at W12 and then every 4 weeks), ustekinumab (uste) (6mg/kg IV at W0 and 90mg SC dose at W8 and then every 8 weeks), or placebo (PBO). This analysis compared clinical response by Patient Reported Outcome (PRO) (30% decrease in SF and/or AP with neither score worse than W0), clinical remission by PRO (SF≤3 and not worse than W0 and AP ≤1 and no worse than W0), change from baseline (CFB) in SF, and in AP up to W12 in miri/PBO randomized patients. Results: Baseline characteristics were balanced across the miri (N=579) and PBO (n=199) treatment groups. A greater proportion of the pts on miri achieved clinical response by PRO at W4, W6, W8, and W12, and clinical remission by PRO at W6, W8, and W12 vs PBO. Miri resulted in significant improvements in SF at W6, W8, and W12, and in AP at W4, W6, W8, and W12 vs PBO (Table 1). The overall safety was consistent with the known safety profile of miri. Most common treatment-emergent adverse events (TEAEs) during induction period in miri-treated pts: COVID-19, anemia, and headache. There were lower frequencies of SAEs (miri: 5.9%, PBO: 9.0%) and discontinuations due to adverse events (miri: 2.4%, PBO:4.7%) in miri-treated pts vs PBO. There were no malignancies, no major adverse cardiovascular events (MACEs), no Hy’s law cases or deaths in the miri arm up to W12. One death was reported in the induction period in the PBO group. Conclusion: In pts with moderately to severely active CD, miri induction was associated with higher rates of clinical response, clinical remission and greater improvement in AP as early as W4, SF as early as W6 vs PBO. Increasing treatment effect was observed through W12. Table 1. - Outcome of mirikizumab induction on clinical response, clinical remission, stool frequency and abdominal pain Clinical response by PROa n (%) Clinical remission by PROa n (%) Stool Frequency (CFB)b LSM (SE) Abdominal Pain (CFB)b LSM (SE) MiriN=579 PBON=199 MiriN=579 PBON=199 MiriN=579 PBON=199 MiriN=579 PBON=199 Week 2 224 (38.7) 75 (37.7) 41 (7.1) 10 (5.0) -1.24 (0.076) -1.24 (0.129) -0.38 (0.022) -0.31 (0.036) Week 4 308 (53.2)* 87 (43.7) 90 (15.5) 27 (13.6) -1.74 (0.087) -1.42 (0.146) -0.55 (0.026)* -0.43 (0.043) Week 6 376 (64.9)*** 100 (50.3) 150 (25.9)* 36 (18.1) -2.20 (0.091)* -1.81 (0.153) -0.72 (0.028)*** -0.52 (0.047) Week 8 404 (69.8)**** 101 (50.8) 175 (30.2)** 37 (18.6) -2.43 (0.096)** -1.85 (0.162) -0.80 (0.029)**** -0.56 (0.049) Week 12 409 (70.6)**** 103 (51.8) 216 (37.3)**** 44 (22.1) -2.65 (0.101)**** -1.86 (0.171) -0.90 (0.031)**** -0.61 (0.052) Footnotes: aNonresponder imputation was used. bModified baseline observation carried forward was used.*refers to P < 0.05 significance; ** refers to P < 0.01 significance; *** refers to P < 0.001 significance; **** refers to P < 0.0001 significance.Abbreviations: AP =abdominal pain; CDAI= Crohn’s Disease Activity Index; CFB=change from baseline; PRO=Patient Reported Outcome (2 of the patient-reported items of the CDAI, AP and SF); LSM=least square mean; SE=standard error; SF=stool frequency; miri=mirikizumab; PBO=placebo.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».