International Journal of Hematology

DOI: 10.1007/s12185-018-2499-y Pages: 70-78

Inhibitor development, safety, and efficacy of Advate® in previously untreated patients with hemophilia A in a postmarketing surveillance in Japan

1. St. Marianna University School of Medicine Yokohama City Seibu Hospital, Department of Pediatrics

2. Tokyo Medical University Hospital, Department of Laboratory Medicine

3. Nagoya University Hospital, Department of Transfusion Medicine

4. Nara Medical University, Department of Pediatrics

5. Japanese Red Cross Society Tokai-Hokuriku Block Blood Center

6. Shire, Department of Medical Affairs

7. Shire, Department of Clinical Scientific Writing

8. Shire, Department of Biostatistics

9. Kitakyushu Yahatahigashi Hospital

Correspondence to:
Masashi Taki



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.

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