Collecting New Peak and Intermediate Infliximab Levels to Predict Remission in Inflammatory Bowel Diseases.


Journal

Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162

Informations de publication

Date de publication:
01 02 2022
Historique:
received: 27 10 2020
pubmed: 31 3 2021
medline: 1 4 2022
entrez: 30 3 2021
Statut: ppublish

Résumé

The loss of response to infliximab is a challenge for clinicians in the management of inflammatory bowel disease (IBD). Mounting evidence suggests that therapeutic drug monitoring at induction may predict remission during maintenance. The aim of the study was to improve predictive models of remission by exploring new peak and intermediate infliximab measurements during induction. This was a prospective multicenter study evaluating the pharmacokinetics of infliximab during induction in a pioneer cohort of 63 patients with IBD. Pharmacokinetics data including peak, intermediate, and trough levels were combined with clinical and biological parameters and were subsequently fed into tailored logistic regression and tree-based techniques to predict remission at week 30. Infliximab peak levels at week 2, intermediate levels at week 3, and trough levels at week 6 were correlated with remission at week 30. Predictive models exhibited an increased accuracy over the successive timepoints of the induction with key inputs such as albumin, C-reactive protein, eosinophils, neutrophils, lymphocytes, intermediate level at week 3, trough level at week 6, and age at diagnosis. Our predictive model of remission at week 30 was obtained with an area under the receiver operating characteristic curve of 0.9 ± 0.12, a sensitivity of 89%, and a specificity of 75%. This study showed the clinical relevance of measuring new infliximab levels to predict remission in patients with IBD. These findings lay the foundation for a personalized medicine in which biotherapies could be monitored at an early stage, thereby improving patients' clinical management.

Sections du résumé

BACKGROUND
The loss of response to infliximab is a challenge for clinicians in the management of inflammatory bowel disease (IBD). Mounting evidence suggests that therapeutic drug monitoring at induction may predict remission during maintenance. The aim of the study was to improve predictive models of remission by exploring new peak and intermediate infliximab measurements during induction.
METHODS
This was a prospective multicenter study evaluating the pharmacokinetics of infliximab during induction in a pioneer cohort of 63 patients with IBD. Pharmacokinetics data including peak, intermediate, and trough levels were combined with clinical and biological parameters and were subsequently fed into tailored logistic regression and tree-based techniques to predict remission at week 30.
RESULTS
Infliximab peak levels at week 2, intermediate levels at week 3, and trough levels at week 6 were correlated with remission at week 30. Predictive models exhibited an increased accuracy over the successive timepoints of the induction with key inputs such as albumin, C-reactive protein, eosinophils, neutrophils, lymphocytes, intermediate level at week 3, trough level at week 6, and age at diagnosis. Our predictive model of remission at week 30 was obtained with an area under the receiver operating characteristic curve of 0.9 ± 0.12, a sensitivity of 89%, and a specificity of 75%.
CONCLUSIONS
This study showed the clinical relevance of measuring new infliximab levels to predict remission in patients with IBD. These findings lay the foundation for a personalized medicine in which biotherapies could be monitored at an early stage, thereby improving patients' clinical management.

Identifiants

pubmed: 33783494
pii: 6203394
doi: 10.1093/ibd/izab042
doi:

Substances chimiques

Gastrointestinal Agents 0
Infliximab B72HH48FLU

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

208-217

Informations de copyright

© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Claire Liefferinckx (C)

Department of Gastroenterology, Hôpital Erasme, ULB, Brussels, Belgium.

Jérémie Bottieau (J)

Department of Electrical Engineering, University of Mons, Mons, Belgium.

Jean-François Toubeau (JF)

Department of Electrical Engineering, University of Mons, Mons, Belgium.

Debby Thomas (D)

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

Jean-François Rahier (JF)

Department of Gastroenterology, CHU UCL Namur, Yvoir, Belgium.

Edouard Louis (E)

Department of Gastroenterology, Centre Hospitalier Universitaire Sart-Tilman, ULG, Liège, Belgium.

Filip Baert (F)

Department of Gastroenterology, AZ Delta, Roeselare-Menen-Torhout, Belgium.

Pieter Dewint (P)

Department of Gastroenterology, AZ Maria Middelares, Ghent, Belgium.
Department of Gastroenterology, UZ Antwerp, Antwerp, Belgium.

Lieven Pouillon (L)

Department of Gastroenterology, Imelda General Hospital, Bonheiden, Belgium.

Guy Lambrecht (G)

Department of Gastroenterology, AZ Damiaan, Oostende, Belgium.

François Vallée (F)

Department of Electrical Engineering, University of Mons, Mons, Belgium.

Severine Vermeire (S)

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Peter Bossuyt (P)

Department of Gastroenterology, Imelda General Hospital, Bonheiden, Belgium.

Denis Franchimont (D)

Department of Gastroenterology, Hôpital Erasme, ULB, Brussels, Belgium.

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