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Pharmacokinetic-pharmacodynamic model of vedolizumab for targeting endoscopic remission in patients with Crohn disease : posthoc analysis of the LOVE-CD study
ID
Hanžel, Jurij
(
Author
),
ID
Dressen, Erwin
(
Author
),
ID
Vermeire, Séverine
(
Author
),
ID
Löwenberg, Mark
(
Author
),
ID
Hoentjen, Frank
(
Author
),
ID
Bossuyt, Peter
(
Author
),
ID
Clasquin, Esmé
(
Author
),
ID
Baert, Filip J.
(
Author
),
ID
D'Haens, Geert R.
(
Author
),
ID
Mathôt, Ron
(
Author
)
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Abstract
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.
Language:
English
Keywords:
therapeutic drug monitoring
,
exposure-response
,
pharmacometrics
,
inflammatory bowel disease
,
Crohn's disease
,
drug clearance
,
endoscopy
,
pharmacodynamics
,
infusion procedures
,
disease remission
,
vedolizumab
,
therapy
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
MF - Faculty of Medicine
Publication status:
Published
Publication version:
Version of Record
Year:
2022
Number of pages:
Str. 689-699
Numbering:
Vol. 28, iss. 5
PID:
20.500.12556/RUL-141904
UDC:
616.3
ISSN on article:
1536-4844
DOI:
10.1093/ibd/izab143
COBISS.SI-ID:
67785475
Publication date in RUL:
11.10.2022
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73
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Record is a part of a journal
Title:
Inflammatory bowel diseases
Shortened title:
Inflamm. bowel dis.
Publisher:
Oxford University Press, Crohn’s & Colitis Foundation
ISSN:
1536-4844
COBISS.SI-ID:
519035417
Licences
License:
CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
Link:
http://creativecommons.org/licenses/by-nc/4.0/
Description:
A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.
Secondary language
Language:
Slovenian
Keywords:
farmakometrika
,
kronična vnetna črevesna bolezen
,
vedolizumab
,
Crohnova bolezen
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