title: Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease.
abstract: BACKGROUND
  Reasons for infliximab failure in Crohn's disease and ulcerative colitis are debated. Serum levels of infliximab and anti-infliximab antibodies have been associated with loss of response. We aimed at determining cut-off levels for infliximab and anti-infliximab antibody concentrations associated with clinical response to infliximab maintenance therapy.
  
  
  METHODS
  Patients with inflammatory bowel disease (n = 106) were retrospectively classified as having maintained response or loss of response to infliximab maintenance therapy. Trough concentrations were measured by fluid-phase radioimmunoassays.
  
  
  RESULTS
  Infliximab levels were significantly lower, and anti-infliximab antibody levels significantly higher, in Crohn's disease patients with loss of response (median infliximab 0 μg/ml, median anti-infliximab antibodies 35 U/ml) compared to patients with maintained response (median infliximab 2.8 μg/ml, median anti-infliximab antibodies 0 U/ml; p < 0.0001). Receiver operating characteristic (ROC) analysis identified optimal cut-off values: infliximab <0.5 μg/ml, which was associated with loss of response with sensitivity 86% [64-97] and specificity 85% [72-94]; and anti-infliximab antibodies ≥10 U/ml yielding a sensitivity of 81% [61-93] and specificity 90% [79-96]. Combined measurements of infliximab and anti-infliximab antibodies using these cut-off values had higher accuracy yielding a sensitivity of 81% [57-94] and specificity 94% [82-98]. Similar pattern was observed in a smaller cohort of patients with ulcerative colitis.
  
  
  CONCLUSIONS
  Combined measurements of infliximab and anti-infliximab antibodies using cut-off levels provided high accuracy for discriminating between clinical response types to infliximab maintenance therapy. Cut-off levels are considered a prerequisite to further investigations of clinical usefulness of measurements of infliximab and anti-infliximab antibodies in patients failing infliximab therapy.
authors.affiliation: Department of Medical Gastroenterology, University Hospital of Copenhagen, Herlev Hospital, Herlev, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Steenholdt
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Jørn
authors.initials: J
authors.lastname: Brynskov
authors.forename: Ole Østergaard
authors.initials: OØ
authors.lastname: Thomsen
authors.forename: Mark Andrew
authors.initials: MA
authors.lastname: Ainsworth
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D011863:Radioimmunoassay; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D017211:Treatment Failure
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000069285:Infliximab