Early Infliximab Trough Levels Predict the Long-term Efficacy of Infliximab in a Randomized Controlled Trial in Patients with Active Crohn’s Disease Comparing, between CT-P13 and Originator Infliximab

Abstract

Background/Aims: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn's disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab. Methods:Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes. Results:The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission. Conclusions:A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.

Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

“…48,49 Table 1 provides an overview of infliximab target concentrations identified from prospective studies and post hoc analysis of RCTs during both induction and maintenance therapy. 10,13,[86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] Post hoc analysis of the pivotal ACCENT I and ACCENT II trials in CD showed that infliximab trough concentrations $3.5 and $7.2 mg/L at week 14 were predictive of clinical response at week 54 and combined fistula response and CRP normalization (composite remission) at week 14, respectively. 10,86 Also, infliximab trough concentrations $20.2 mg/L at week 2 and $15 mg/L at week 6 were associated with composite complete remission at week 14.…”