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

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• 作者：David Ternant ; Zahir Berkane ; Laurence Picon…
• 刊名：Clinical Pharmacokinetics
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：54
• 期：5
• 页码：551-562
• 全文大小：612 KB
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  20.Dall’Ozzo S, T
• 作者单位：David Ternant (1) (3)
  Zahir Berkane (1) (3)
  Laurence Picon (4)
  Valérie Gouilleux-Gruart (1) (5)
  Jean-Frédéric Colombel (6)
  Matthieu Allez (7)
  Edouard Louis (8)
  Gilles Paintaud (1) (3)
  
  1. Université Fran?ois Rabelais de Tours, CNRS UMR 7292, 2 Boulevard Tonnellé, 37044, Tours, CEDEX, France
  3. Laboratory of Pharmacology-Toxicology, CHRU de Tours, Tours, France
  4. Department of Gastroenterology, CHRU de Tours, Tours, France
  5. Department of Immunology, CHRU de Tours, Tours, France
  6. Icahn School of Medicine at Mount Sinai, New York, NY, USA
  7. Service de Gastroentérologie, INSERM Unit U940 (Avenir), H?pital Saint-Louis, APHP, Université Denis Diderot, Paris, France
  8. University Hospital, CHU of Liège, Liège, Belgium
  
• 刊物主题：Pharmacotherapy; Pharmacology/Toxicology; Internal Medicine;
• 出版者：Springer International Publishing
• ISSN：1179-1926

文摘

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???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.