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Title: Antibody Response to Infliximab and its Impact on Pharmacokinetics can be Transient
Authors: Vande Casteele, Niels ×
Gils, Ann
Singh, Sharat
Ohrmund, Linda
Hauenstein, Scott
Rutgeerts, Paul
Vermeire, Severine #
Issue Date: Jun-2013
Publisher: Nature Publishing Group
Series Title: The American journal of gastroenterology vol:108 issue:6 pages:962-971
Article number: 10.1038/ajg.2013.12
Abstract: OBJECTIVES: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.Am J Gastroenterol advance online publication, 19 February 2013; doi:10.1038/ajg.2013.12.
URI: 
ISSN: 0002-9270
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Therapeutic and Diagnostic Antibodies (+)
× corresponding author
# (joint) last author

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