OP035 Efficacy and safety of abrilumab (AMG 181/MEDI 7183) therapy for moderate to severe Crohn's disease
Notice bibliographique
Résumé
Background: Adhesion molecule α4β7 is a validated treatment target in inflammatory bowel diseases. We evaluated abrilumab, a fully human monoclonal antibody against α4β7, in patients with moderate to severe Crohn's disease (CD). Methods: This phase 2b, randomised, multi-centre, double-blind, placebo (Pbo)-controlled study enrolled patients aged 18–65 years with moderate to severe CD (CDAI score 220–450) and evidence of active inflammation (by endoscopic evaluation, or elevated C-reactive protein or fecal calprotectin). In addition, patients must have had inadequate or loss of response or intolerance to immunosuppressives, TNF antagonists, or corticosteroids. Eligible patients were randomised to receive Pbo or abrilumab (21 or 70 mg) SC on day 1, weeks 2 and 4, and every 4 weeks (Q4W) for up to 24 weeks, or one dose of abrilumab 210 mg SC on day 1. The primary endpoint was CDAI remission (score <150) at week 8. Key secondary endpoints were remission at week 12 and CDAI response (reduction from baseline of ≥100) at weeks 8 and 12. CD4+ T cell subsets were enumerated and α4β7 receptor occupancy was measured in a subgroup of patients. Results: This study enrolled 249 patients. Final randomisation allocation was affected by a systematic misalignment in investigational product, resulting in 98, 26, 84, and 41 patients in the Pbo, 21 mg Q4W, 70 mg Q4W, and 210 mg treatment groups, respectively. The study blind and randomisation were intact. Baseline demographics were similar. Statistically significant improvement was not achieved between the abrilumab 70 mg Q4W and Pbo arms for the primary endpoint (p=0.76 vs Pbo) (Table). However, higher rates of remission and response were observed in the active treatment arms at week 12, particularly in patients with prior failure of TNF antagonists assigned to the 210 mg abrilumab group. Maximal reduction of free α4β7 on naïve CD4+ T cells in the peripheral blood was sustained from the first measurement at week 2 to week 8 for all dose groups, and through week 12 for the 21 mg Q4W and 70 mg Q4W groups. Abrilumab induced a significant post-dose increase in α4β7-high central memory CD4+ T cell counts between baseline and week 8. Adverse events were similar among treatment groups through week 24, with no cases of PML or deaths. No patients developed neutralizing antibodies to abrilumab. Conclusions: Although the primary endpoint was not met, beneficial effects of abrilumab were observed for remission and response rates. There was no safety imbalance compared with Pbo. Amgen and AstraZeneca/MedImmune sponsored this study.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».