title: Anti-infliximab antibodies are already detectable in most patients with rheumatoid arthritis halfway through an infusion cycle: an open-label pharmacokinetic cohort study.
abstract: BACKGROUND
  This study in patients with rheumatoid arthritis (RA) treated with infliximab describes prospectively the course of (anti)infliximab levels within an infusion cycle to assess at what moment patients develop low/no infliximab trough levels and/or detectable anti-infliximab levels.
  
  
  METHODS
  Infliximab treated RA patients were included in this descriptive open-label cohort study. During one infusion cycle (anti-)infliximab levels were assessed just before and one hour after infusion, and subsequently at 50%, 75% and at the end of the infusion cycle (pre-infusion).
  
  
  RESULTS
  27 patients were included. The median infliximab levels decreased from 77.0 mg/l (p25-p75: 65-89) one hour after the infusion to pre-infusion levels of 0.0 mg/l (p25-p75: 0.0-3.1). In 7 (26%) patients pre-infusion anti-infliximab antibodies were detected; these antibodies were already present halfway through the infusion cycle in 5 of the 7 individuals. Patients with detectable pre-infusion anti-infliximab antibodies have significantly more often low/no infliximab levels (< 1 mg/l) halfway trough the infusion cycle (in 5/7 patients) compared to patients without detectable pre-infusion anti-infliximab antibodies (0/20 patients, p < 0.001).
  
  
  CONCLUSIONS
  Most anti-infliximab forming patients have detectable anti-infliximab antibodies halfway through an infusion cycle, which implies that these patients are exposed to nontherapeutical infliximab levels during more than half of their infusion cycle. As none of the patients without anti-infliximab antibodies had no/low-infliximab levels halfway through the infusion cycle, the presence of pre-infusion anti-infliximab antibodies seems a sensitive and specific predictor for no/low infliximab-levels.
authors.affiliation: Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands. b.vandenbemt@maartenskliniek.nl
authors.forename: Bart J F
authors.initials: BJ
authors.lastname: van den Bemt
authors.forename: Alfons A
authors.initials: AA
authors.lastname: den Broeder
authors.forename: G J
authors.initials: GJ
authors.lastname: Wolbink
authors.forename: Yechiel A
authors.initials: YA
authors.lastname: Hekster
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Bart
authors.initials: B
authors.lastname: Benraad
authors.forename: Frank H J
authors.initials: FH
authors.lastname: van den Hoogen
mesh_terms: D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology* / Q000493:pharmacokinetics; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000276:immunology* / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015331:Cohort Studies; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab