Pharmacokinetic-pharmacodynamic model of vedolizumab for targeting endoscopic remission in patients with Crohn disease : posthoc analysis of the LOVE-CD study

Hanžel, Jurij (avtor), Dressen, Erwin (avtor), Vermeire, Séverine (avtor), Löwenberg, Mark (avtor), Hoentjen, Frank (avtor), Bossuyt, Peter (avtor), Clasquin, Esmé (avtor), Baert, Filip J. (avtor), D'Haens, Geert R. (avtor), Mathôt, Ron (avtor)

Background: Higher serum concentrations of vedolizumab have been associated with improved outcomes in inflammatory bowel disease. It is unclear how vedolizumab exposure is linked to endoscopic remission in Crohn disease (CD). We aimed to develop a pharmacokinetic-pharmacodynamic model linking vedolizumab exposure to endoscopic remission in CD. Methods: Data were obtained from the first 110 patients participating in a phase 4 prospective multicenter trial (LOVE-CD; ClinicalTrials.gov identifier: NCT02646683), where vedolizumab was dosed at 300 mg every 8 weeks and serum concentrations and antibodies to vedolizumab were measured before each infusion. Concentration-time profiles were described by a 2-compartment model with parallel linear and nonlinear elimination. A first-order discrete-time Markov model was used to describe the relationship between pharmacokinetic exposure metrics and the probability of endoscopic remission (Simple Endoscopic Score for CD < 4). Results: Linear clearance was 0.215 L/d, and the volume of distribution of the central compartment was 4.92 L. Linear clearance was higher and vedolizumab exposure was lower in patients with lower serum albumin concentrations, in the presence of antibodies to vedolizumab, and in patients with previous exposure to other biologic therapy. A week 22 vedolizumab concentration of 20.0 mg/L was predicted to yield a 35% probability of achieving endoscopic remission at week 26. Model-based simulations suggested that endoscopic remission rates of 46.5% or 40.0% could be reached with every-4-weeks dosing in patients who were naïve or previously exposed to biologic therapy, respectively. Conclusions: Model-informed dosing of vedolizumab in CD provides a foundation for future research aiming to maximize endoscopic remission rates.

• Jezik: Angleški jezik
• Ključne besede: therapeutic drug monitoring, exposure-response, pharmacometrics, inflammatory bowel disease, Crohn's disease, drug clearance, endoscopy, pharmacodynamics, infusion procedures, disease remission, vedolizumab, therapy
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 689-699
• Številčenje: Vol. 28, iss. 5
• PID: 20.500.12556/RUL-141904
• UDK: 616.3
• ISSN pri članku: 1536-4844
• DOI: 10.1093/ibd/izab143
• COBISS.SI-ID: 67785475
• Datum objave v RUL: 11.10.2022

Gradivo je del revije

• Naslov: Inflammatory bowel diseases
• Skrajšan naslov: Inflamm. bowel dis.
• Založnik: Oxford University Press, Crohn’s & Colitis Foundation
• ISSN: 1536-4844
• COBISS.SI-ID: 519035417

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: farmakometrika, kronična vnetna črevesna bolezen, vedolizumab, Crohnova bolezen