OC 27.4 - Wide Individual variation of emicizumab concentrations and surrogate factor VIII activity assessed by human factor-based chromogenic substrate assay in hemophilia A patients without inhibitor

Sunday, June 23, 2024

15:30 – 15:45 ICT

Room: 210 A-D

Presenting Author(s)

Masato Bingo, MD, PhD

Assistant Professor
Department of Laboratory medicine, Tokyo Medical University
Shinjukuku, Tokyo, Japan

Co-Author(s)

Azusa Nagao, MD, MSc, PhD

Stuff physician
Department of Blood Coagulation, Ogikubo Hospital
Tokyo, Tokyo, Japan
Yoshiyuki Ogawa

Assistant Professor
Department of Hematology, Gunma University Graduate School of Medicine
Maebashi, Gumma, Japan
HU

Haruka Uemura

Stuff physician
AIDS Clinical Center, National Center for Global Health and Medicine
Shinjuku, Tokyo, Japan
JI

Junji Imamura

Stuff physician
Department of Infectious Diseases, National Hospital Organization Sendai Medical Center
Sendai, Miyagi, Japan
KF

Katsuyuki Fukutake

Chair of Department
Department of Blood Coagulation, Ogikubo Hospital
Suginamiku, Tokyo, Japan
HH

Hiroshi Handa

Associate Professor
Department of Hematology, Gunma University Graduate School of Medicine
Maebashi, Gumma, Japan
TI

Toshihiro Ito

Chair of Department
Department of Infectious Diseases, National Hospital Organization Sendai Medical Center
Sendai, Miyagi, Japan
Keiko Shinozawa, PhD

Assistant Professor
Department of Laboratory Medicine, Tokyo Medical University/Japan
Shinjuku-ku, Tokyo, Japan
Hiroshi Inaba

Associate Professor
Department of Laboratory Medicine, Tokyo Medical University
Shinjuku, Tokyo, Japan
EK

Ei Kinai

Professor
Department of Laboratory Medicine, Tokyo Medical University
Shinjuku, Tokyo, Japan

Background: Emicizumab has become widely used for people with hemophilia A (PwHA), however, laboratory coagulation assay for emicizumab is yet to be developed. We previously validated the quantitativity of surrogate FVIII activity of emicizumab using human factor-based chromogenic substrate assay (hCSA) by in vitro settings, and here report a clinical validation study using Japanese PwHA without inhibitor with emicizumab (CANADE study, jRCTs031210222).

Aims: To evaluate individual variation of emicizumab concentration and surrogate FVIII activity by hCSA in real-world settings.

Methods: We recruited 50 PwHA without inhibitor treated with emicizumab at doses of 1.5mg/kg QW, 3mg/kg Q2W and 6mg/kg Q4W between August 2021 and March 2023. Patient characteristics data and measurement data of emicizumab concentration and reported FVIII activity by hCSA were collected.

Results: Forty-nine participants were included for analysis. The median age of study cohort was 44 (range: 21-73), 46 had severe and 3 had moderate hemophilia, and the median body mass index was 22.78 (range: 16.36-38.92). Emicizumab was administered QW in 12 participants, Q2W in 33, and Q4W in 4. The emicizumab concentration varied widely with a median (range) of 52.5 μg/mL (12.4-111) (Figure 1), and of note, standard concentration (40-60 μg/mL) was observed in only 17 (34.7%) of patients. There was a significant correlation between emicizumab plasma concentration and reported FVIII activity by hCSA (r= 0.91 and p=1.47e-19). The median (range) of surrogate FVIII activity was 22.7 (7.1-43.4) IU/dL, and lower and higher surrogate FVIII activity ( < 10% and >30%) were observed in 3 (6.1%) and 13 (26.5%), respectively (Figure 2).

Conclusion(s): There was a wide individual variation of emicizumab concentration and surrogate FVIII activity under standard treatment. Because hCSA-based reported FVIII activity strictly correlates with emicizumab concentration, hCSA seems to be an easy-to-access and precise monitoring assay for PwHA using emicizumab.