1. Inhibitor development, safety and efficacy of Advate® among previously treated patients with hemophilia A in a postmarketing surveillance in Japan
- Author
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Katsuyuki Fukutake, Hiroshi Takagi, Werner Engl, Junki Takamatsu, Tadashi Matsushita, Morio Arai, Midori Shima, Akira Shirahata, Haruhiko Uchikawa, Keiji Nogami, Akira Yoshioka, and Masashi Taki
- Subjects
medicine.medical_specialty ,Hematology ,business.industry ,Immunogenicity ,Significant difference ,Postmarketing surveillance ,Recombinant factor viii ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,symbols ,Family history ,Previously treated ,business ,Fisher's exact test ,030215 immunology - Abstract
Rurioctocog alfa (recombinant Factor VIII: AdvateⓇ) is available for the control of bleeding in patients with hemophilia A in Japan. To evaluate the immunogenicity, safety, and efficacy of prophylactic and on-demand use of rurioctocog alfa, postmarketing surveillance was conducted on 114 previously untreated Japanese patients aged 0–82 years with ≤ 3 exposure days under the conditions of routine clinical practice. A post-hoc comparison of mean annualized bleeding rates between patients in the regular prophylaxis group (7.4 bleeds/year) and in the on-demand treatment group (15.7 bleeds/year) using a negative binomial model found a statistically significant difference (P = 0.0164) in the subset of patients with severe hemophilia A. Favorable prophylactic and on-demand hemostatic efficacy (“excellent” or “good”) was shown in 71.4–88.5% across all treatment regimens. A total of 31 events of adverse drug reactions were reported. Of 114 patients, 21 (18.4%) developed de novo FVIII inhibitor; of these, 17 occurred within 50 exposures. One death was reported. A family history of positive inhibitors was significantly associated with inhibitor development (Fisher exact P value = 0.0004); no other risk factors were identified. Rurioctocog alfa was found to be well-tolerated and effective in previously untreated Japanese patients with hemophilia A in this postmarketing surveillance of routine clinical practice.
- Published
- 2019