dc.contributor.author
Grisic, Ana‐Marija
dc.contributor.author
Eser, Alexander
dc.contributor.author
Huisinga, Wilhelm
dc.contributor.author
Reinisch, Walter
dc.contributor.author
Kloft, Charlotte
dc.date.accessioned
2021-04-28T06:20:42Z
dc.date.available
2021-04-28T06:20:42Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/30564
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-30304
dc.description.abstract
Aim
Quantitative and kinetic insights into the drug exposure‐disease response relationship might enhance our knowledge on loss of response and support more effective monitoring of inflammatory activity by biomarkers in patients with inflammatory bowel disease (IBD) treated with infliximab (IFX). This study aimed to derive recommendations for dose adjustment and treatment optimisation based on mechanistic characterisation of the relationship between IFX serum concentration and C‐reactive protein (CRP) concentration.
Methods
Data from an investigator‐initiated trial included 121 patients with IBD during IFX maintenance treatment. Serum concentrations of IFX, antidrug antibodies (ADA), CRP, and disease‐related covariates were determined at the mid‐term and end of a dosing interval. Data were analysed using a pharmacometric nonlinear mixed‐effects modelling approach. An IFX exposure‐CRP model was generated and applied to evaluate dosing regimens to achieve CRP remission.
Results
The generated quantitative model showed that IFX has the potential to inhibit up to 72% (9% relative standard error [RSE]) of CRP synthesis in a patient. IFX concentration leading to 90% of the maximum CRP synthesis inhibition was 18.4 μg/mL (43% RSE). Presence of ADA was the most influential factor on IFX exposure. With standard dosing strategy, ≥55% of ADA+ patients experienced CRP nonremission. Shortening the dosing interval and co‐therapy with immunomodulators were found to be the most beneficial strategies to maintain CRP remission.
Conclusions
With the generated model we could for the first time establish a robust relationship between IFX exposure and CRP synthesis inhibition, which could be utilised for treatment optimisation in IBD patients.
en
dc.format.extent
11 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
C‐reactive protein remission
en
dc.subject
inflammatory bowel disease
en
dc.subject
infliximab dosing
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
Quantitative relationship between infliximab exposure and inhibition of C‐reactive protein synthesis to support inflammatory bowel disease management
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1111/bcp.14648
dcterms.bibliographicCitation.journaltitle
British Journal of Clinical Pharmacology
dcterms.bibliographicCitation.number
5
dcterms.bibliographicCitation.pagestart
2374
dcterms.bibliographicCitation.pageend
2384
dcterms.bibliographicCitation.volume
87
dcterms.bibliographicCitation.url
https://doi.org/10.1111/bcp.14648
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie

refubium.funding
DEAL Wiley
refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1365-2125