RT Journal Article
SR Electronic
T1 The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1539
OP 1545
DO 10.1136/gutjnl-2014-307883
VO 64
IS 10
A1 Niels Vande Casteele
A1 Reena Khanna
A1 Barrett G Levesque
A1 Larry Stitt
A1 G Y Zou
A1 Sharat Singh
A1 Steve Lockton
A1 Scott Hauenstein
A1 Linda Ohrmund
A1 Gordon R Greenberg
A1 Paul J Rutgeerts
A1 Ann Gils
A1 William J Sandborn
A1 Séverine Vermeire
A1 Brian G Feagan
YR 2015
UL http://gut.bmj.com/content/64/10/1539.abstract
AB Objective Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab.Design In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission.Results Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission.Conclusions The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed.