Population Pharmacokinetics and Dose De‐Escalation Regimens of Subcutaneous Vedolizumab in Inflammatory Bowel Disease
S. I. Anjie, N. Vreman, K. B. Gecse, M. Löwenberg, G. R. D'Haens, R. A. A. MathôtABSTRACT
Background
Vedolizumab is a therapeutic antibody approved for the treatment of Crohn's disease and ulcerative colitis. The population pharmacokinetics (popPK) of intravenous (IV) administered vedolizumab have been described, but remain to be defined for subcutaneous (SC) administration.
Aims
To develop a popPK model for SC vedolizumab and to evaluate, through simulation, whether extended dosing intervals maintain adequate serum concentrations in patients with quiescent IBD receiving maintenance treatment.
Methods
Real‐world data of patients receiving IV vedolizumab who were subsequently switched to SC administration every 2 weeks (SC‐Q2W), were prospectively collected. Nonlinear mixed effects modeling (NONMEM) was applied to develop the popPK model. Extension of the SC‐Q2W regimen was evaluated through simulation.
Results
Data from 61 patients (43 CD and 18 UC) was available with a total of 225 serum samples (IV: 129, SC: 96). Data was described by a two‐compartment model with parallel linear and nonlinear elimination using prior PK information. A patient with a body weight of 70 kg, serum albumin of 40 g/L and serum white blood cell count of 7 × 10 9 /L had a linear clearance (CL L ) of 0.157 L/day. Interindividual variability of CL L was 22.9% and was dependent on body weight, serum albumin, and white blood cell count. Upon SC‐Q2W dosing, patients with trough levels > 42.4 mg/L (18%) and > 60.3 mg/L (2%) could be de‐escalated to Q3W and Q4W dosing, respectively, while achieving a trough concentration of at least 26 mg/L.
Conclusions
The popPK model adequately described SC vedolizumab PK. Simulation suggests that extended dosing intervals may be feasible. Prospective clinical studies are required to evaluate clinical implications of dose de‐escalation.