P529 Exposure–response relationship of vedolizumab subcutaneous treatment in patients with ulcerative colitis: VISIBLE 1
Notice bibliographique
Résumé
Vedolizumab is a gut-selective, humanised, monoclonal α4β7 integrin antibody approved for intravenous (IV) administration to treat adult patients with moderate–severe ulcerative colitis (UC). The VISIBLE 1 study assessed the efficacy and safety of a novel vedolizumab formulation for subcutaneous (SC) administration in adult patients with moderate–severe UC. We report the exposure–response and immunogenicity results for vedolizumab SC vs. vedolizumab IV. Pharmacokinetic (PK) and exposure–response data for vedolizumab IV are published.1,2 VISIBLE 1 (NCT02611830) was a Phase 3, double-blind, double-dummy, randomised, placebo-controlled trial. After open-label vedolizumab IV induction treatment (300 mg IV at Weeks [Weeks] 0 and 2), patients with a clinical response at WK6 were randomised to maintenance treatment with placebo, vedolizumab 108 mg every 2 weeks SC, or vedolizumab 300 mg every 8 weeks IV. PK serum samples were taken at prespecified time points. Descriptive statistics were used to summarise vedolizumab PK and immunogenicity using a drug-tolerant electrochemiluminescence assay. Vedolizumab trough concentrations (Ctrough) at WK46 (the final comparable trough sample) were grouped by quartiles and clinical outcome rates were calculated. A total of 216 patients were randomised to placebo (n = 56), vedolizumab SC (n = 106), and vedolizumab IV (n = 54). Both higher vedolizumab SC Ctrough and vedolizumab IV Ctrough concentrations were associated with greater efficacy at WK52, with improved response for low-exposure patients in the SC arm. An increase in WK52 clinical remission was observed in both arms, from 50% to 83% of patients in SC and from 18% to 90% in IV. An increase in WK52 mucosal healing was observed in 50% to 89% of patients in SC and 27% to 100% of patients in IV. A similar trend was observed for both predicted steady-state average concentration and troughs. WK52 exposure–response results for vedolizumab IV were generally comparable with GEMINI 1 results. [1] Immunogenicity was similar for vedolizumab SC and IV and was not associated with injection-site or hypersensitivity reactions. Exposure–response relationships in VISIBLE 1 were similar to those seen previously in GEMINI 1.1,2 Higher serum concentrations of vedolizumab with SC and IV administration during maintenance therapy are associated with greater proportions of patients achieving clinical remission and mucosal healing. Figure 1. Week 52 vedolizumab SC efficacy according to Ctrough quartiles. References 1. Rosario M, Dirks NL, Milch C, et al. A review of the clinical pharmacokinetics, pharmacodynamics, and immunogenicity of vedolizumab. Clin Pharmacokinet 2017;56:1287-1301. 2. Feagan BG, Rutgeerts P, Sands BE et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013;369:699–710.
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 ».