Evaluation of pharmacokinetic metrics and pharmacodynamic biomarkers associated with endoscopic healing in pediatric Crohn's disease patients treated with anti-tumor necrosis factor biologics.
In a multicenter cross-sectional cohort of 87 patients aged 1–22 years with Crohn’s disease receiving infliximab or adalimumab, lower CD64 biomarkers and slower infliximab clearance were associated with endoscopic healing, while anti-TNF trough concentrations were not.
Open original publication →What the AI sees
In a multicenter cross-sectional cohort of 87 patients aged 1–22 years with Crohn’s disease receiving infliximab or adalimumab, lower CD64 biomarkers and slower infliximab clearance were associated with endoscopic healing, while anti-TNF trough concentrations were not.
Research significance
The reported associations suggest—but do not establish—that combining infliximab clearance with CD64 and routine laboratory biomarkers could help distinguish inadequate pharmacokinetic exposure from persistent pharmacodynamic disease activity, potentially informing dose escalation versus switching therapy after prospective validation.
Source abstract
BACKGROUND: Crohn's disease (CD) patients achieving deep remission, defined as clinical remission with endoscopic healing (EH), have a lower rate of CD-related adverse events. EH can be achieved with anti-tumor necrosis factor (TNF) dose optimizations directed by pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers. The primary aim was to identify PK metrics and PD biomarker cut-points associated with EH. METHODS: In this multicenter, cross-sectional study, we enrolled CD patients (age 1-22 years) who received an anti-TNF biologic (infliximab or adalimumab) for >6 months and underwent ileocolonoscopy. EH was defined as a simple endoscopic score-CD (SES-CD) < 3. RESULTS: Eighty-seven patients were enrolled with EH found in 55.2%. Lower levels of novel biomarkers neutrophil CD64, monocyte CD64, and soluble CD64 were associated with EH with cut-points of <4.5 ratio (AUROC 0.76), <44.6 ratio (AUROC 0.67), and <15.9 ng/mL (AUROC 0.67), respectively. There was no difference in the mean trough concentrations of infliximab or adalimumab between EH and non-EH, but the median infliximab clearance was higher in non-EH (0.26 L/day) compared to EH (0.21 L/day, P = .02). In our infliximab multivariable model, slower infliximab clearance, lower platelet count, and higher serum albumin were strong predictors for EH (AUC 0.90). CONCLUSIONS: We identified novel PK and PD cut-points for biomarkers associated with EH, including infliximab clearance and the novel CD64 biomarkers. Furthermore, we developed a multivariable PK and PD model for EH that, following validation, could guide dose escalation (PK failures) or prompt a switch to an alternate advanced therapeutic for PD failures.