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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 5/2015

01-05-2015 | Original Research Article

Assessment of the Influence of Inflammation and FCGR3A Genotype on Infliximab Pharmacokinetics and Time to Relapse in Patients with Crohn’s Disease

Authors: David Ternant, Zahir Berkane, Laurence Picon, Valérie Gouilleux-Gruart, Jean-Frédéric Colombel, Matthieu Allez, Edouard Louis, Gilles Paintaud

Published in: Clinical Pharmacokinetics | Issue 5/2015

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Abstract

Background and Objectives

Infliximab is a monoclonal anti-tumor necrosis factor-α (anti-TNFα) antibody that profoundly modified the treatment of Crohn’s disease (CD). The polymorphism of Fc fragment of IgG, low affinity IIIa, receptor (CD16a) [FCGR3A] influences the biological response to infliximab in patients with CD. Our aim was to study its influence on infliximab pharmacokinetics and risk of relapse after infliximab discontinuation.

Methods

In 111 CD patients in remission, infliximab was discontinued and its concentrations were measured for 30 months or until relapse. Infliximab pharmacokinetics were described using monocompartmental population modeling.

Results

The elimination rate of infliximab increased with C-reactive protein (CRP) [p = 0.00018] and was 16 % higher in FCGR3A-158V/V patients than in F carriers (p = 0.0028). Risk of relapse was higher in patients with baseline CRP ≥5 mg/L than in those with a lower value (p = 0.0000029). In addition, there was a first-order interaction between CRP and the FCGR3A genotype; in patients with high CRP, risk of relapse was higher for V/V patients than for F carriers (hazard ratio 4.80 and 2.84 for V/V and F carriers, respectively; p = 0.013).

Conclusion

Both increased inflammation and FCGR3A-158V/V genotype are associated with increased infliximab elimination and risk of relapse after infliximab discontinuation in patients with CD.
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Metadata
Title
Assessment of the Influence of Inflammation and FCGR3A Genotype on Infliximab Pharmacokinetics and Time to Relapse in Patients with Crohn’s Disease
Authors
David Ternant
Zahir Berkane
Laurence Picon
Valérie Gouilleux-Gruart
Jean-Frédéric Colombel
Matthieu Allez
Edouard Louis
Gilles Paintaud
Publication date
01-05-2015
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 5/2015
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-014-0225-3

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