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Longitudinal dynamic changes in factor VIII inhibitor titers in patients with hemophilia A and inhibitors receiving emicizumab prophylaxis

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Abstract

Emicizumab prophylaxis dramatically reduces bleeding events in patients with hemophilia A (PwHA) with or without factor VIII (FVIII) inhibitors. However, long-term dynamic changes in FVIII inhibitor titers during emicizumab prophylaxis remain to be investigated. We conducted a retrospective follow-up study of FVIII inhibitor titers after initiation of emicizumab prophylaxis in 25 PwHA carrying current or historical FVIII inhibitors. Nineteen PwHA had FVIII inhibitors at initiation of emicizumab prophylaxis (age: median 22 [range 4–60] years and inhibitor titer: 30 [1.0–1450] BU/mL). In 17 of the 19 patients, the inhibitor titers markedly decreased to a median of 1.2 (< 0.6–58) BU/mL at a median follow-up of 71 (38–111) months. In two patients, titers were slightly elevated after initiation of emicizumab but decreased in the long term. The remaining six patients had negative inhibitor status (< 0.6 BU/mL) when switched to emicizumab from FVIII prophylaxis. Five patients maintained negative titers. One patient had inhibitor recurrence, with a peak titer of 1.6 BU/mL that decreased to 0.9 BU/mL. In most cases, FVIII inhibitor titers can be expected to decrease spontaneously during emicizumab prophylaxis, but regular follow-up is necessary to manage breakthrough bleeds.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Ms. Nanako Omichi for technical support.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pediatrics, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8522, Japan

    Naruto Shimonishi, Kana Sasai, Kenichi Ogiwara, Shoko Furukawa, Yuto Nakajima, Kuniyoshi Mizumachi, Koji Yada, Masahiro Takeyama, Midori Shima & Keiji Nogami

  2. The Course of Thrombosis and Hemostasis Molecular Pathology, Nara Medical University, Kashihara, Nara, Japan

    Naruto Shimonishi & Midori Shima

  3. Advanced Medical Science of Thrombosis and Hemostasis, Nara Medical University, Kashihara, Nara, Japan

    Yuto Nakajima & Midori Shima

  4. Division of Hemophilia, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Koji Yada

  5. Chugai Pharmaceutical Co., Ltd., Tokyo, Japan

    Narumi Mizuno

Authors
  1. Naruto Shimonishi
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  2. Kana Sasai
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  3. Kenichi Ogiwara
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  4. Shoko Furukawa
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  7. Koji Yada
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  8. Masahiro Takeyama
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  9. Midori Shima
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  10. Narumi Mizuno
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  11. Keiji Nogami
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Contributions

NS designed all the experiments, analyzed and interpreted the data, constructed the figures and tables, wrote the manuscript, and approved the final version to be published. KS measured the inhibitor titers. KO, KY, SF, YN, KM, and MT supported the clinical work. MS supported the clinical study and supervised the study. NM interpreted the data. KN designed all the experiments, analyzed and interpreted the data, constructed the figures and tables, wrote the manuscript, and edited the manuscript.

Corresponding author

Correspondence to Naruto Shimonishi.

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Conflict of interest

N. Shimonishi taught a course endowed by the CSL Behring. K. Sasai has no conflicts of interest to declare. K. Ogiwara received personal fees from Chugai Pharmaceutical Co. Ltd. taught a course endowed by CSL Behring. K. Yada taught a course endowed by the Shire Plc and Takeda Pharmaceutical Co., Ltd. S. Furukawa received personal fees from Chugai Pharmaceutical Co., Ltd., and taught a course endowed by CSL Behring. Y. Nakajima received a grant from Takeda Pharmaceutical Co. Ltd. K. Mizumachi has no conflict of interest to disclose. M. Takeyama received personal fees from Chugai Pharmaceutical Co., Ltd., KM Biologics Co., Bayer AG, and CSL Behring. M. Shima has received grants, personal fees, and non-financial support from Chugai Pharmaceutical Co., Ltd.; personal fees from F. Hofmann-La Roche Ltd.; personal fees and non-financial support from Sysmex Co.; grants from Takeda Pharmaceutical Co., Sanofi S. A., CSL Behring Co., KM Biologics Co., and Novo Nordisk A/S; personal fees from Bayer AG, Bioverativ Inc., and BioMarin Pharmaceutical Inc.; and is an inventor of the patents related to emicizumab. N. Mizuno is an employee of Chugai Pharmaceutical Co., Ltd. K. Nogami has received grants, personal fees, and non-financial support from Chugai Pharmaceutical Co., Ltd.; personal fees from F. Hofmann-La Roche Ltd.; grants, personal fees, and non-financial support from Sysmex Co. and Sekisui Medical; grants and personal fees from Takeda Pharmaceutical Co.; grants and personal fees from Sanofi S.A; personal fees from CSL Behring Co.; grants and personal fees from KM Biologics Co.; grants and personal fees from Novo Nordisk A/S; grants and personal fees from Bayer AG; grants and personal fees from Bioverativ Inc.; and grants and personal fees from Shire Plc; personal fees from Fujimoto Seiyaku; and is an inventor of the patents related to emicizumab.

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Shimonishi, N., Sasai, K., Ogiwara, K. et al. Longitudinal dynamic changes in factor VIII inhibitor titers in patients with hemophilia A and inhibitors receiving emicizumab prophylaxis. Int J Hematol 118, 690–698 (2023). https://doi.org/10.1007/s12185-023-03667-y

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  • DOI: https://doi.org/10.1007/s12185-023-03667-y

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