2020
DOI: 10.1111/bcp.14364
|View full text |Cite
|
Sign up to set email alerts
|

Modelling of the relationship between infliximab exposure, faecal calprotectin and endoscopic remission in patients with Crohn's disease

Abstract: Aims: Evidence for the benefits of pharmacokinetic (PK) and pharmacodynamic (PD) monitoring of infliximab in patients with Crohn's disease (CD) remains scarce. We aimed to develop a population (pop)PK/PD model to characterise the infliximab dose-exposure-biomarker-response (faecal calprotectin [fCal] and endoscopic remission [ER]) relationship. Methods: Data were obtained from 116 patients with CD in a phase 4 doseescalation study. Three sequential models were developed: a 2-compartment popPK model linking inf… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

3
5
0

Year Published

2020
2020
2024
2024

Publication Types

Select...
10

Relationship

4
6

Authors

Journals

citations
Cited by 21 publications
(8 citation statements)
references
References 52 publications
3
5
0
Order By: Relevance
“…Although the mechanism of action is different (anti-TNF versus anti-IL12/23), a similar dose-exposure-fCal-endoscopic remission sequence has been modelled for infliximab in biological-naïve patients with active luminal CD. 36 The median fCal observed at baseline was similar between our study (1398 μg/g) and the infliximab study (1462 μg/g). The maximum drug effect on the production rate constant of fCal was fixed to 100% in both popPK-PD models.…”
Section: Discussionsupporting
confidence: 80%
“…Although the mechanism of action is different (anti-TNF versus anti-IL12/23), a similar dose-exposure-fCal-endoscopic remission sequence has been modelled for infliximab in biological-naïve patients with active luminal CD. 36 The median fCal observed at baseline was similar between our study (1398 μg/g) and the infliximab study (1462 μg/g). The maximum drug effect on the production rate constant of fCal was fixed to 100% in both popPK-PD models.…”
Section: Discussionsupporting
confidence: 80%
“…This integration holds the potential to establish patientspecific therapeutic targets, offering an additional avenue alongside MIPD tools. 9 In this regard, we agree with the notion that population PKPD models have the potential to surpass current population PK models within the realm of MIPD. This shift can facilitate model-informed joint drug-biomarker monitoring, ultimately aiming to enhance therapeutic success.…”
Section: To the Editorssupporting
confidence: 85%
“…For biologics, common factors that have been shown to affect drug clearance include sex, body weight, serum albumin, inflammatory burden, immunogenicity, concomitant immunomodulation, and polymorphisms in the neonatal Fc receptor. 149,150 By applying population pharmaco kinetic models, previous and concurrent drug concentration measurements can be used to predict the timing or magnitude of future doses required to reach a prespecified drug concentration. Such methods are referred to as dashboards.…”
Section: Pharmacokinetic Modelling and Dashboardsmentioning
confidence: 99%