PB0621 - : Emicizumab plasma concentrations are not related to bleeding rates using standard dosing, a call for dose adaptation

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

Konrad van der Zwet, MD

MD|PhD-Candidate
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University
Utrecht, Utrecht, Netherlands

Co-Author(s)

Lv

Lize F.D. van Vulpen

Internist Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands
Pv

Paul R. van der Valk

Internist Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands
Idske C.L Kremer Hovinga, MD PhD

Pediatric Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands
Karin P. M. van Galen, MD PhD MsC

Internist Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Utrecht, Utrecht, Netherlands
Roger E.G Schutgens, MD, PhD, MSc (he/him/his)

Internist-hematologist, Professor
Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht and University Utrecht, Utrecht, The Netherlands
Utrecht, Utrecht, Netherlands

Presenting Author(s)

Kathelijn Fischer, MD, PhD (she/her/hers)

Pediatric Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands

Background: Prophylaxis with emicizumab results in highly effective bleed prevention in persons with hemophilia A (PWHA), but it is high cost limits widespread access. Data from the HAVEN-trials and several small case series suggest that bleeding control is adequate at low emicizumab concentrations and/or dosing below the standard dosing of 6 mg/kg/4weeks.

Aims: To correlate emicizumab plasma concentrations with bleeding rates in PWHA using standard dosing.

Methods: In this monocenter observational cohort, consecutive PWHA receiving emicizumab ≥4 weeks were included. Emicizumab was dosed according to label (± 6mg/kg/4weeks, rounded to vials) at 1-4 weekly intervals. Data on treated bleeds and emicizumab concentrations in maintenance phase was extracted from electronic patient files January 2021 to December 2022. Emicizumab concentrations were routinely measured, at least annually, using a validated mass spectrometry-method. Emicizumab concentrations groups were categorized in quartiles (Q1-Q4). Mean annualized (joint) bleeding rates (A(J)BR) were estimated and compared across quartiles of emicizumab concentrations groups using negative binomial regression modelling.

Results: 127 patients were included, 8% had an active inhibitor and 93% had severe hemophilia A. The median age at start of emicizumab was 23.3 years (range: 0.5 – 78.3) and duration of therapy was 1.8 years (IQR 1.2 – 2.2).
The median emicizumab plasma concentration during maintenance was 61.2 µg/ml (IQR 45.4 – 75.0). The overall mean ABR was 0.61 (95CI 0.46 – 0.80) and mean AJBR was 0.29 (95CI 0.21 – 0.41). The mean A(J)BR rate was low across the quartiles of emicizumab (Table 1). A(J)BR did not decrease with higher emicizumab concentrations, and 95CI showed overlap.

Conclusion(s): This large observational cohort confirmed low annualized (joint) bleeding rates on emicizumab prophylaxis. Bleeding rates did not correlate with emicizumab plasma concentrations, suggesting no added value of higher emicizumab concentrations and/or dosing.