PS1487 EFFECT OF PLASMA EXCHANGE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF CAPLACIZUMAB

Abstract

Background:During clinical trials in patients with acquired thrombotic thrombocytopenic purpura, caplacizumab was administered as a 10 mg intravenous (iv) bolus prior to plasma exchange (PE), followed by 10 mg daily subcutaneous (sc) doses during the daily PE period and at least 30 days thereafter.Aims:The potential effect of different time intervals between the first iv bolus and the subsequent PE, and the effect of different PE schedules, have been investigated.Methods:An integrated pharmacokinetic (PK)/pharmacodynamic (PD) model was developed to describe the interaction between caplacizumab and vWF using non‐linear mixed effects modeling and used to simulate the resulting PK and PD for different predetermined scenarios:1) PE start 3, 5, 11, 23 h post‐caplacizumab 10 mg iv bolus2) PE schedule: daily and twice per day (bid) at the first day or during 7 daysResults:Data from clinical trials indicate complete neutralization of vWF activity for caplacizumab peak plasma concentrations ≥500ng/mL. Simulations suggest that median caplacizumab peak plasma levels would remain above this threshold if the PE starts up to 5 h post‐caplacizumab iv bolus. For longer delays median caplacizumab peak plasma levels can fall below 500ng/mL, and an additional 10 mg sc dose prior to PE can maintain an effective drug exposure.Simulations of the effect of a bid PE for 7 days, suggest that the sc dosing schedule of caplacizumab during the PE period could be adjusted with bid 10 mg caplacizumab sc dosing after each PE treatment during the time of bid PE treatment.Summary/Conclusion:Effective drug levels are expected if PE is started up to 5 h following the first iv dose of caplacizumab. For longer delays, an additional 10 mg sc dose prior to PE can be envisaged.In case of bid PE for 7 days, the sc administration schedule of caplacizumab could be adjusted with bid caplacizumab after each PE treatment.