title: Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease.
abstract: BACKGROUND
  The aim of the study was to investigate variations in anti-infliximab (IFX) antibody (Ab) levels and clinical implications thereof in patients with inflammatory bowel disease (IBD).
  
  
  METHODS
  A retrospective, explorative, single-center study of patients with IBD who developed anti-IFX Ab and in whom anti-IFX Ab were reassessed.
  
  
  RESULTS
  IFX was administered to 316 patients; anti-IFX Ab was determined in 180 patients and detected in 83 (46%). During ongoing IFX maintenance therapy, anti-IFX Ab disappeared at later reassessment in two-thirds of patients with clinical response after median 4 (3-5) infusions. In contrast, anti-IFX Ab persisted in all patients without clinical response. Anti-IFX Ab appeared pharmacologically active, as IFX levels were high when anti-IFX Ab disappeared (median 3.7 μg/mL, interquartile range [IQR] 2.8-5.5), while undetectable or low when anti-IFX Ab persisted (median 0 μg/mL, IQR 0-0). In 56 patients, anti-IFX Ab were assessed after IFX discontinuation. The proportion of patients with anti-IFX Ab gradually declined over time, with a few patients having anti-IFX Ab up to about 4 years after initial assessment. No variables were associated with anti-IFX Ab disappearance in multivariate analysis.
  
  
  CONCLUSIONS
  Discontinuation of IFX is advisable in patients with inadequate response and repeat positive anti-IFX Ab measurements. Anti-IFX Ab can persist for years after discontinuation, which could impact efficacy and safety at retreatment. Continued IFX treatment may, however, be considered in patients with clinical response and a single positive anti-IFX Ab measurement, as anti-IFX Ab disappears in two-thirds of these during continued treatment.
authors.affiliation: Department of Medical Gastroenterology, Herlev Hospital, Herlev, Denmark. steenholdt@brygge.dk
authors.forename: Casper
authors.initials: C
authors.lastname: Steenholdt
authors.forename: Magid
authors.initials: M
authors.lastname: Al-khalaf
authors.forename: Jørn
authors.initials: J
authors.lastname: Brynskov
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Ole Ø
authors.initials: OØ
authors.lastname: Thomsen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ainsworth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology*; D000069285:Infliximab; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab