Background and Importance Understanding determinants of vedolizumab clearance may enhance treatment optimisation as there are limited data on therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD).

Aim and Objectives The objective of this study was to perform a preliminary pharmacokinetic (PK) model of vedolizumab in real-life to evaluate covariates potentially responsible for the PK variability in adult patients with IBD.

Material and Methods A 5-year retrospective unicentre study was performed including adults (>18 years) diagnosed with IBD and treated with intravenous vedolizumab. Demographic and clinical data were collected, including serum albumin, C reactive protein (CRP) and faecal calprotectin (FCal). Vedolizumab trough levels (VTL) were obtained before administrations. Vedolizumab concentrations and anti-vedolizumab antibodies (AVA) were determined by ELISA. The model was developed in NONMEM v7.4 by approximating the non-linear mixed effects models. The first order conditional estimation method with interaction (FOCEI) was used for model building. Body weight (WGT) was included in PK parameters following an allometric relationship.

Results Sixty-one patients (27 women) were included, 34 (56%) were diagnosed with ulcerative colitis and 27 (44%) with Crohn’s disease. Median age (range) was 43 (IQR:35–59) years and weight 70.9 (CI 95%: 67.2–74.7) kg. A total of 101 concentrations were determined, with a median concentration of 25.9 (IQR:10.4–47.1) µg/mL. Median serum albumin, CRP and FCal levels were: 4.5 (IQR: 4.2–4.7)g/dL, 3.6 (IQR:1.3–8.0) mg/dL and 404.2 (IQR:105.3–1329) μg/g, respectively. Any patient has developed AVA. Population PK model (PopPK): a one compartment with first order elimination described adequately the VTL. Among the clinical variables analysed, none was found significant on clearance (CL) and distribution volume (Vd). The final PopPK model in the absence of AVA was as defined as: V=4.55L and CL(L/day)=0.15 (WGT/70kg)^0.75. Interindividual variability associated with CL (IIVCL) from 14.2%. Proportional residual error estimated was 15.1%.

Conclusion and Relevance Vedolizumab PK in adult patients with IBD was best described by a one compartment model with first order elimination. WGT was included in CL, following an allometric relationship. Further investigation is required in order to find possible covariates and validate this PK model.

References and/or Acknowledgements 1. Rosario M, et al. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn’s disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188–202.

Conflict of Interest No conflict of interest.