Safety of Recombinant von Willebrand Factor in the Treatment of von Willebrand Disease: Real-World Data from an EU Post-Authorization Safety Study.

Introduction: In Europe, recombinant von Willebrand factor (rVWF) is approved for the prevention and treatment of hemorrhage or surgical bleeding in adults with von Willebrand disease (VWD) for whom desmopressin alone is ineffective or contraindicated. Real-world data on rVWF safety are limited. Aim: To assess the safety of rVWF in real-world European clinical practice. Methods: EU post-authorization safety study (NCT05265078, EUPAS45617) was a multicenter, retrospective, non-interventional study conducted in adults with VWD who received rVWF at 1 of 30 participating sites in Europe (January 2019-March 2023). Data were collected retrospectively for ≥7 days and ≤6 months after the first rVWF infusion, and similarly, after each subsequent rVWF course. Primary outcomes were the risk of hypersensitivity reactions, thromboembolic events, and VWF/factor VIII (FVIII) inhibitor formation when used for hemorrhage treatment or prevention/treatment of surgical bleeding; and the association of thromboembolic events with concurrent use of FVIII for hemorrhage treatment or prevention/treatment of surgical bleeding. Results: In the primary analysis, 87 patients received 203 rVWF treatment courses. In total, 2 hypersensitivity-related AEs of mild severity occurred in 1 patient who received rVWF (0.00068 events per person-day at risk), and 1 thromboembolic AE of moderate severity (venous thrombosis) was reported in 1 patient (0.00127 events per person-week at risk). There were no reports of VWF or FVIII inhibitor formation. The association between thromboembolic events and the concurrent use of rVWF and FVIII could not be assessed because no patient received rVWF in conjunction with FVIII. Conclusion: In this EU post-authorization safety study, the risks of hypersensitivity reactions and thromboembolic events with rVWF were low and there were no reports of VWF or FVIII inhibitor formation. Overall, no new safety signals were identified in this European real-world study when rVWF was used for the prevention or treatment of hemorrhage or surgical bleeding in VWD.