title: Assessment of the Influence of Inflammation and FCGR3A Genotype on Infliximab Pharmacokinetics and Time to Relapse in Patients with Crohn's Disease.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université François Rabelais de Tours, CNRS UMR 7292, 2 Boulevard Tonnellé, 37044, Tours, CEDEX, France, david.ternant@univ-tours.fr.
authors.forename: David
authors.initials: D
authors.lastname: Ternant
authors.forename: Zahir
authors.initials: Z
authors.lastname: Berkane
authors.forename: Laurence
authors.initials: L
authors.lastname: Picon
authors.forename: Valérie
authors.initials: V
authors.lastname: Gouilleux-Gruart
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D000069285:Infliximab / Q000493:pharmacokinetics*; D008297:Male; D015337:Multicenter Studies as Topic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*; D012008:Recurrence
chemical_list: C496124:FCGR3A protein, human; D017452:Receptors, IgG; D002097:C-Reactive Protein; D000069285:Infliximab