Therapeutic antibody clearance reliable predictor for endoscopic outcomes in CD

Monoclonal antibody clearance may better predict endoscopic improvement than trough concentrations in patients with Crohn’s disease (CD) on infliximab or ustekinumab. The first remains a reliable predictor regardless of dose optimisation or bodyweight dose corrections, whereas the latter appears to lose its predictive ability with these adjustments.

Dr Erwin Dreesen (KU Leuven, Belgium) and co-investigators hypothesised that therapeutic antibody clearance is a reliable predictor of endoscopic outcomes in patients with CD [1]. Participants in the TAILORIX cohort who were treated with the monoclonal antibodies infliximab (n=108) or ustekinumab (n=80) were assessed for therapeutic antibody clearance [1,2]. “We relied on therapeutic antibody dosing, the covariates body weight and serum albumin, and 1 therapeutic drug monitoring [TDM] sample for the determination of clearance,” explained Dr Dreesen. “We used Bayesian forecasting to calculate clearance [fCAL], and this process was TDM-based and population pharmacokinetics [popPK]-model-informed.” The goal was to observe whether clearance can predict endoscopic response. “For patients on infliximab, we used endoscopic remission at week 12 and week 54, and for patients on ustekinumab, we used endoscopic response at week 24 as the outcome.”

Trough concentrations (AUC 0.64) and antibody clearance (AUC 0.62) were equally accurate at predicting endoscopic outcomes in patients who received infliximab induction therapy. However, while antibody clearance preserved its predictive accuracy during maintenance therapy (AUC 0.63), trough concentration (AUC 0.50) appeared less reliable as a predictor for endoscopic outcomes. fCAL had the best predictive values for infliximab induction (AUC 0.70) and maintenance therapy (AUC 0.67).

In ustekinumab users, antibody clearance appeared to perform equally well as fCAL and slightly better than trough concentrations during induction (AUC 0.67 vs 0.65 vs 0.59) and maintenance therapy (AUC 0.70 vs 0.70 vs 0.63). A software tool to calculate clearance in clinical practice is in development, and Dr Dreesen showed a beta-version of this modality during his presentation.

“TDM-based, popPK-model-informed monoclonal antibody clearance outperformed trough concentrations when predicting endoscopic outcomes in CD,” concluded Dr Dreesen. “While trough concentrations lost their predictive ability when they were manipulated by dose optimisations [for infliximab] or weight-based dosing corrections [for ustekinumab], antibody clearance remained a reliable predictor.”

1. Wang Z, et al. Therapeutic antibody clearance better predicts endoscopic outcomes than trough concentrations in patients with Crohn’s disease. OP12, 20th Congress of ECCO, 19–22 February 2025, Berlin, Germany.
2. D'Haens G, et al. Gastroenterology. 2018;154(5):1343-1351.e1.

Copyright ©2025 Medicom Medical Publishers



Posted on 8 April 20258 April 2025