Clinical efficacy and safety of von Willebrand factor concentrate almost devoid of factor VIII in long-term prophylaxis study in patients older than 6 years with severe von Willebrand disease

Background Benefits of long-term prophylaxis (LTP) in patients with severe von Willebrand disease (VWD) were well established by several studies. However, data on treatment modalities to gain optimal dosing and infusion schedule are limited. Objectives To assess the efficacy and safety of LTP with a plasma-derived von Willebrand factor (pdVWF, Wilfactin®) compared with on-demand treatment in patients over 6 years of age. Design Prospective, non-controlled, open-label, multicentre study. Methods Patients with basal plasma VWF:RCo levels <20 IU/dL received pdVWF for LTP for ≥1 year. The dose was individualised according to the history of bleeding pattern (either mucosal or non-mucosal) and pharmacokinetic data. The primary efficacy endpoint was the annualised bleeding rate (ABR) for each bleeding pattern. A secondary endpoint included response for all bleeds. Results Seven patients with type 3 VWD completed the study. The median duration of prophylactic treatment was 2.6 years. One patient was treated to prevent gastrointestinal bleeds and no haemorrhage was reported. Six patients were placed on LTP to prevent recurrent bleeds. Median ABR according to the bleeding category was 1.1 in 3 patients having predominantly non-mucosal bleeds and 4.2 in 3 other patients with mucosal bleeds representing a reduction of 82.5% and 67.5% respectively. One patient in each category had no spontaneous bleed the first year of prophylaxis. Including all bleeds in all patients, median ABR decreased from 52 to 4.3, representing an 83.3% reduction (95% confidence interval: 35.58%, 92.95%). No safety concern was identified. Conclusion Prophylactic treatment using a pdVWF was safe and effective in clinically severe VWD.