Optimizing Therapies Using Therapeutic Drug Monitoring: Current Strategies and Future Perspectives

Real world population pharmacokinetic study in children and young adults with inflammatory bowel disease discovers novel blood and stool microbial predictors of vedolizumab clearance

“…Among the prospective cohort, patients with SFCR at infusion‐4 had higher median infusion‐3 vedolizumab cTrough, median 49 μg/ml, 37–56 compared to patients who did not achieve clinical remission with a median trough of 26 μg/ml (15–27; p = 0.013; Figure 4A). Similarly, patients with SFCR also maintained higher cTrough at infusion‐4, median 27 μg/ml, 22–31 compared to patients not in SFCR (median 13.4 μg/ml; 7.7–20.3; p = 0.016; Figure 4B).…”

“…These covariates have been incorporated into a vedolizumab population PK model that can be used to individualise vedolizumab dosing in this patient population. Using the new model in a simulation analysis of standard vedolizumab infusions (0, 2 and 6 weeks followed by every 8 weeks), we demonstrate that the expected cTrough at week 22 (infusion‐5) in the majority of patients would result in drug exposure below current cTrough targets 28,29 . We further found that interval shortening had a greater impact on achieving higher attainment of target rates compared to weight‐based dose escalation.…”

“…Simulations ( n = 1000) with the final model were performed to investigate the influence of the different maintenance intervals and PK covariate predictors on steady‐state maintenance (weeks 21–24) target attainment rates, with a preselected target of 15 or 20 μg/mL 8,27–29 . Two types of simulations were conducted.…”

“…Additional simulation analyses ( n = 1000) were performed to study how various dosing intervals and the identified PK covariates in the population model would affect target attainment rates of previously published maintenance cTrough targets ≥15–20 μg/ml, which were reported to be associated with endoscopic remission 8,27–29 …”

“…Baseline patient and disease characteristics are outlined in Table 1. The median peak concentration was 109 μg/ml (88-128), while the median cTrough was 25 μg/ml (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Only one patient had incidental ATV measured at 363 ng/ml at infusion-2 which resolved (undetectable) without any intervention by infusion-3.…”