Rationale for Investigator-Assigned Prophylaxis Dosing Frequency in the Leopold I Study

The LEOPOLD I study (part B) in severe hemophilia A was a multicenter, phase II/III, open-label trial to assess the safety, tolerability, and efficacy of prophylaxis treatment with BAY 81-8973, an unmodified recombinant factor VIII product. Dose and dose frequency of the prophylaxis regimen during the study were at the investigators' discretion. A questionnaire was sent to sites poststudy to determine what elements led to the assignment of patients to a twice-weekly regimen rather than 3 times weekly. Seventeen specific questions were posed, plus 1 labeled as "other," allowing the investigator to insert a rationale not otherwise specified.

Responses to the questionnaire were received for 13 of 17 patients (76%) assigned to twice-weekly prophylaxis. The 2 most frequent responses were "treatment options were discussed with the patients" (67%) and "patient preference" (61%). Additional responses in descending frequency included "prophylaxis regimen was adapted to the patient's physical activity and schedule" (28%) and "already on a twice-weekly regimen before the study," "sedentary lifestyle," "noncompliance with a 3-times-weekly regimen," and "other" (17% each). "Minimal arthropathy," "no target joints," and "patient's age" were included at 11% each.

These results demonstrate that discussions between patient and doctor are appropriately considered paramount to treatment decisions. The other elements mentioned are known parameters thought to contribute to bleeding phenotype in hemophilia.