Abstract
Rurioctocog alfa (recombinant factor VIII: Advate®) is available for the control of bleeding among patients with hemophilia A in Japan. To evaluate the perioperative safety and hemostatic efficacy of Advate®, a postmarketing surveillance was conducted in Japanese patients undergoing surgery in a real-world setting. A total of 74 surgical procedures performed in 58 subjects aged 0–75 years, including three females, were studied. A hemostatic efficacy rating of “excellent” or “good” was reported in 73/74 surgical procedures (98.6%). Perioperative bleeding was successfully controlled by Advate® in five subjects with positive FVIII inhibitors (2.4-9.1 BU/mL). Advate® was administered at higher initial bolus doses (114-385 IU/kg) and at higher rates by subsequent initial continuous infusion (8.3-15 IU/kg/hour) in the five subjects with inhibitor than in the subjects without inhibitor (n = 47; mean initial bolus dose: 53.4 IU/kg; subsequent mean initial continuous infusion: 3.8 IU/kg/h). Adverse drug reactions were reported in 7/74 (9.5%) procedures, two of which were the development of de novo FVIII inhibitors. Overall, the perioperative use of Advate® in a real-world setting was found to be safe and effective among Japanese patients with hemophilia A.
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Notes
The increase in FVIII inhibitor titers was coded into two discrete serious ADRs (i.e., FVIII inhibition and condition aggravated) by the sponsor, which was reported in the reexamination application of Advate® PMS (a special investigation on surgery).
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Acknowledgements
This manuscript is dedicated to the memory of our esteemed colleague Dr. Hideji Hanabusa, MD, whose untimely passing away in October 2016 left a permanent void. He touched the lives of many as a mentor, scholar, collaborator, and friend. Dr. Hanabusa was instrumental in the development of this product, and the creation and interpretation of the data included herein, and a co-author of this manuscript. We thank Shire PMS and PV teams for the support in data clarification. We recognize with gratitude the patients and institutions that participated in the studies: IMSUT Hospital, Institute of Medical Science, The University of Tokyo; Nara Medical University Hospital; Tokyo Medical University Hospital; St. Marianna University School of Medicine Hospital; Nagoya University Hospital; Ogikubo Hospital; Hospital of the University of Occupational and Environmental Health; Kurume University Hospital; Hyogo College of Medicine Hospital; Mie University Hospital.
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KN, HT, MS, AY, TM, JT, MT, KF, and AS collected and interpreted data, and revised the manuscript. WE analyzed the statistics, interpreted data, and revised the manuscript. HU, HT, and MA interpreted data and drafted and revised the manuscript. All authors had full editorial control of the manuscript and provided their written approval forms for the content of the manuscript.
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Keiji Nogami has received grants from Baxalta and funding for research from Baxalta, Bayer, Novo Nordisk, Bioverativ, Chugai, and honoraria from Baxalta, Bayer, Novo Nordisk, Bioverativ, CSL Behring, and Chugai outside the submitted work. Hideyuki Takedani has received honoraria from Baxalta/Shire, Bayer, Biogen, Bioverativ, Chugai Pharmaceutical, CSL Behring, Kaketsuken, Novo Nordisk, and Pfizer and has received a grant from CSL Behring. Midori Shima has received personal fees and grants from Baxalta Bayer, Novonordisk, CSL Behring, Chugai, and Pfizer; personal fees from Bioverativ and Roche; grants from Kaketsuken outside the submitted work. Akira Yoshioka has received honoraria from Baxalta, Japan Red Cross, Daiichi Sankyo, and Bayer outside the submitted work. Tadashi Matsushita has received personal fees from Baxalta for the submitted work, grants and personal fees from Bayer, Baxalta, Novo Nordisk, Kaketsuken, and Biogen-idec outside the submitted work. Junki Takamatsu has declared no conflict of interest. Masashi Taki is an advisory board member for Bioverativ, Chugai, CSL Behring, and Novo Nordisk and an investigator in clinical trials conducted by Baxalta/Shire, Bioverativ, Chugai, CSL Behring, Novo Nordisk, and Octapharma; has received research supports from CSL Behring and speaker’s fee from Baxalta/Shire, Bayer, Bioverativ, Novo Nordisk, and Pfizer. Katsuyuki Fukutake has received grants and personal fees from Baxalta outside the submitted work and holds concurrent posts as a professor for the Department of Molecular Genetics of Coagulation Disorders supported by CSL Behring without additional salary; is an advisory committee member of Chugai Pharmaceutical, and consultant of Chugai Pharmaceutical; has received research funding from Bayer, Biogen/Bioverativ, Kaketsuken, Novo Nordisk, and Pfizer; has received honoraria for consulting, speaking or advising from Bayer, Biogen/Bioverativ, Chugai Pharm./Roche, CSL Behring, Japan Blood Products, Kaketsuken, MSD, Novo Nordisk, Octapharma, and Pfizer. Akira Shirahata has declared no conflict of interest. Werner Engl, Haruhiko Uchikawa, Hiroshi Takagi, and Morio Arai are full-time employees of Shire (formerly Baxalta).
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Nogami, K., Takedani, H., Shima, M. et al. Perioperative safety and hemostatic efficacy of Advate® in patients with hemophilia A in a postmarketing surveillance in Japan. Int J Hematol 108, 22–29 (2018). https://doi.org/10.1007/s12185-018-2434-2
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DOI: https://doi.org/10.1007/s12185-018-2434-2