title: Antibody response to infliximab and its impact on pharmacokinetics can be transient.
abstract: OBJECTIVE
  Infliximab (IFX) is successfully used in the treatment of inflammatory bowel diseases but some patients generate antibodies to IFX (ATI) jeopardizing the pharmacokinetics of the drug. Little is known about the factors influencing ATI formation and whether or not this immune reaction is permanent. Our aim was to investigate the kinetics of ATI formation and drug levels in relation to inflammatory markers and the clinical evolution of the patients.
  
  
  METHODS
  IFX trough and ATI levels were measured retrospectively in 1,232 consecutive serum samples of 90 (64 Crohn's disease and 26 ulcerative colitis) patients, 57 with previously detected and 33 without antibodies with a new homogenous mobility shift assay.
  
  
  RESULTS
  Testing with new assay confirmed ATI in 53/90 patients (59%) and 37/90 patients (41%) were ATI negative. In 15/53 patients (28%), ATI disappeared over time whereas in 38/53 patients (72%) ATI persisted. The 26/38 (68%) patients with sustained ATI needed to discontinue IFX treatment compared with 2/15 (13%) patients with transient ATI (relative risk 5.1; 95% confidence interval 1.4-19.0; P=0.0005). An IFX trough level at week 14<2.2 μg/ml predicted IFX discontinuation due to persistent loss of response (LOR) or hypersensitivity reactions with 74% specificity and 82% sensitivity (likelihood ratio 3.1; P=0.0026).
  
  
  CONCLUSIONS
  ATI may be transient and do not always lead to a worse clinical outcome. Sustained high levels of ATI, however, lead to permanent LOR. Patients with low IFX trough levels at week 14 are at risk for ATI formation and IFX discontinuation. Therefore, we recommend to measure IFX trough levels at week 14 and at time of LOR. When undetectable or low, ATI should be determined and if positive followed up on consecutive time points to rule out sustained ATI.
authors: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. niels.vandecasteele@pharm.kuleuven.be
authors: Niels
authors: N
authors: Vande Casteele
authors: Ann
authors: A
authors: Gils
authors: Sharat
authors: S
authors: Singh
authors: Linda
authors: L
authors: Ohrmund
authors: Scott
authors: S
authors: Hauenstein
authors: Paul
authors: P
authors: Rutgeerts
authors: Séverine
authors: S
authors: Vermeire
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics*; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D012372:ROC Curve; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013997:Time Factors; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D000069285:Infliximab