Journal
CLINICAL PHARMACOKINETICS
Volume 60, Issue 7, Pages 931-941Publisher
ADIS INT LTD
DOI: 10.1007/s40262-021-01006-0
Keywords
-
Categories
Funding
- F. Hoffmann-La Roche Ltd.
- qPharmetra
Ask authors/readers for more resources
This study aimed to describe the relationship between Emicizumab concentrations and bleeding frequency, confirming adequate bleeding control with three different dosing regimens. The results showed that all three Emicizumab dosing regimens maintained concentrations close to the plateau of effect, leading to a significant reduction in annualized bleeding rate.
Background and Objective Emicizumab is a monoclonal antibody that bridges activated coagulation factor IX and factor X to restore effective hemostasis in persons with hemophilia A. It is indicated for routine prophylaxis of bleeding episodes in persons with hemophilia A. The aim of the present study is to describe the exposure-response relationship between emicizumab concentrations and bleeding frequency, and to confirm adequate bleeding control of the investigated dosing regimens 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks. Methods Treated bleeding events were pooled from 445 persons with hemophilia A with and without inhibitors against factor VIII, participating in six clinical studies. Emicizumab concentrations were predicted using a previously developed population pharmacokinetic model. A count model was used to quantify the exposure-response relationship. These models were used to illustrate the relationship between emicizumab concentrations and cumulative count of bleeding over 1 year (annualized bleeding rate). Results The final exposure-response model, based on a generalized Poisson distribution and an inhibitory E-max relationship, adequately describes the relationship between daily emicizumab concentrations and daily bleed frequency. A significant effect of factor VIII prophylaxis among persons with hemophilia A without inhibitors was found. Annualized bleeding rate simulations show that the three emicizumab dosing regimens maintain the concentrations close to the plateau of the effect. At the average steady-state concentration across all regimens (53.5 mu g/mL), the predicted mean annualized bleeding rate is 1.28, corresponding to a 94.0% reduction from baseline. Conclusions These results confirm that average emicizumab concentrations achieved with all three emicizumab dosing regimens provide adequate bleeding control.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available