Pharmacokinetics and Exposure-Response During Infliximab Induction Therapy in Pediatric IBD Using Point-of-Care Assay

Background: Pharmacokinetic therapeutic failure with infliximab during induction therapy can pose a significant challenge for clinicians. The objective of this study was to conduct population pharmacokinetic and exposure-response analyses in children with inflammatory bowel disease during infliximab induction therapy. Methods: A prospective single-center observational study was conducted in anti-TNF naïve pediatric patients < 21 years of age with IBD starting infliximab according to their physicians' clinical judgment between December 2018 and December 2020. Population pharmacokinetic analysis was conducted by nonlinear mixed-effects modeling using infliximab serum levels measured by RIDASCREEN^® enzyme-linked immunosorbent assay. Infliximab serum levels were also measured by point-of-care (POC) assay using RIDA^®QUICK IFX monitoring and the RIDA^®QUICK SCAN II. An exposure-response analysis was conducted to evaluate the association between infliximab concentrations and efficacy outcomes at week 14. Results: The typical value of infliximab clearance in a pediatric patient with IBD weighing 51 kg was 0.252 L/day, and the Vc was 3.43 L and Vp was 2.11 L. Weight and albumin were identified to be significant covariates on clearance in the final model. Tertile analysis of infliximab exposure showed an exposure-response relationship in which higher infliximab ELISA concentrations during induction therapy were associated with clinical remission at week 14 and biochemical response at week 14, but the trend did not reach statistical significance due to the small sample size. The concordance correlation coefficient between the infliximab ELISA and the POC assay was 0.905 [0.867, 0.933]. Conclusions: We report parameter estimates during infliximab induction therapy in pediatric patients with inflammatory bowel disease. Weight and albumin were identified to be significant covariates on clearance. ELISA and POC infliximab assays showed comparable results, supporting the role of POC testing for real-time therapeutic drug monitoring.