Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn's disease who lose clinical response

Dreesen, E.; Van Stappen, T.; Ballet, V.; Peeters, M.; Compernolle, G.; Tops, S.; Van Steen, Kristel; Van Assche, G.; Ferrante, M.; Vermeire, S.; Gils, A.

doi:10.1111/apt.14452

Article (Scientific journals)

Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn's disease who lose clinical response

Dreesen, E.; Van Stappen, T.; Ballet, V. et al.

2018 • In Alimentary Pharmacology and Therapeutics, 47 (3), p. 346-355

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/225151

DOI
10.1111/apt.14452

PubMed
29226370

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Keywords :

Article; Crohn disease

Abstract :

[en] Background: The presence of antibodies towards infliximab (ATI) is associated with lower infliximab (IFX) trough concentrations and loss of response. IFX treatment intensification is effective for restoring response in most, but not all patients with Crohn's disease (CD). Aim: To compare outcome, pharmacokinetics and immunogenicity of treatment intensification strategies in patients with CD who lost clinical response to IFX. Methods: A retrospective cohort study was conducted, including 103 patients with CD who lost clinical response during IFX maintenance therapy and therefore received a double dose IFX (10 mg/kg) and/or a next infusion after a shortened interval. IFX and ATI concentrations were measured in consecutive trough samples, just before (T0) and after (T+1) treatment intensification. Results: Clinical response (physicians' global assessment) and biological response and remission (CRP) were restored in 63%, 42% and 24% of patients (evaluated at T+1). Treatment intensification increased IFX trough concentrations from 1.2 μg/mL [0.3-3.6] at T0 to 3.6 μg/mL [0.5-10.2] at T+1 (P <.0001). Using a drug tolerant assay, ATI were detected in the T0 sample of 47% of patients. ATI negatively impacted the achieved IFX trough concentration (Spearman r −0.57, P <.0001) and the probability of clinical response (P = 0.034) at T+1. When ATI were quantifiable but <282 ng/mL eq. at T0, combined interval shortening and dose doubling was more effective for restoring therapeutic IFX trough concentrations (≥3 μg/mL at T+1) than dose doubling alone, which in turn was more effective than interval shortening alone (P <.001). Conclusion: Antibodies towards infliximab can guide clinical decision-making on treatment intensification. © 2017 John Wiley & Sons Ltd

Research Center/Unit :

UCB Pharma

Disciplines :

Gastroenterology & hepatology

Author, co-author :

Dreesen, E.; Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

Van Stappen, T.; Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

Ballet, V.; Translational Research in GastroIntestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium, Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium

Peeters, M.; Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

Compernolle, G.; Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

Tops, S.; Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

Van Steen, Kristel ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique

Van Assche, G.; Translational Research in GastroIntestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium, Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium

Ferrante, M.; Translational Research in GastroIntestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium, Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium

Vermeire, S.; Translational Research in GastroIntestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium, Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium

Gils, A.; Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

Language :

English

Title :

Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn's disease who lose clinical response

Publication date :

2018

Journal title :

Alimentary Pharmacology and Therapeutics

ISSN :

0269-2813

eISSN :

1365-2036

Publisher :

Blackwell Publishing Ltd

Volume :

Issue :

Pages :

346-355

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

TBM grant number T003716N

Funders :

FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen
Ferring Pharmaceuticals
Celgene
MSD - Meso Scale Diagnostics
LFA - Lupus Foundation of America
KU Leuven - Katholieke Universiteit Leuven
Novartis
BMS - Bristol-Myers Squibb
AbbVie
Pfizer
Chiesi Farmaceutici Spa
VLAIO - Agentschap Innoveren & Ondernemen
Janssen Pharmaceutica
Abbott
MSD - Merck Sharp and Dohme

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