Pharmacokinetic and pharmacodynamic modelling of vedolizumab in Crohn’s disease using summary level data and its application to model-informed precision dosing

OBJECTIVES: To optimize vedolizumab therapy for Crohn's disease, this study aimed to construct a pharmacokinetic/pharmacodynamic (PK/PD) model by applying model-based meta-analysis (MBMA) methods to summary-level clinical data (SLD) and to evaluate a model-informed precision dosing (MIPD) approach based on the model. METHODS: We used the results of previously reported PK analysis. For PD analysis, summary-level Crohn's Disease Activity Index (CDAI) data were extracted from Phase III trials. Following covariate analysis, the final model was fitted using the Markov chain Monte Carlo Bayesian method (four chains; burn-in 10 000; 100 000 sampling) in NONMEM. The final model was leveraged for empirical Bayes estimation in an MIPD case study. KEY FINDINGS: The posterior estimates of the final model indicated adequate between-chain mixing and acceptable precision ($\hat{R}$<1.01; most achieved bulk and tail effective sample size > 1000 with lowest values of 541 and 820, respectively). In the case study, the MIPD approach based on the final model accurately predicted the time course of the CDAI with minimal. CONCLUSION: PK/PD modelling by applying MBMA methods to SLD is feasible when access to individual patient data (IPD) is restricted. The MIPD approach demonstrated promising predictive accuracy. Future confirmatory studies using IPD are warranted to establish impact on patient outcomes.