Real-world treatment characteristics and outcomes in patients with von Willebrand disease treated prophylactically with plasma-derived or recombinant von Willebrand factor in europe: A multi-center, retrospective study

Abstract Introduction Von Willebrand disease (VWD) is an inherited bleeding disorder caused by deficiencies in the concentration, structure, or function of von Willebrand factor (VWF). Treatment strategies include VWF replacement with plasma-derived VWF (pdVWF) concentrates. In Europe, a recombinant VWF (rVWF; Takeda Pharmaceuticals U.S.A., Inc.) is also approved for the prevention and treatment of hemorrhage or surgical bleeding in adults with VWD. There is limited information on the use of rVWF prophylaxis in clinical practice. Here, we describe the real-world clinical characteristics, treatment patterns, and clinical outcomes of patients with VWD receiving prophylaxis with rVWF or pdVWF in Europe. Methods This retrospective chart review was conducted at sites in Germany and France treating patients with VWD prophylactically with rVWF and pdVWF concentrates. Patients with a confirmed VWD diagnosis were eligible if they had received prophylaxis with either rVWF or pdVWF concentrates administered either continuously (at least once weekly for ≥3 consecutive months) or intermittently (at least once per menstrual cycle for ≥3 cycles per year). Eligible patients also had to be ≥18 years old at the time of the index date. For patients receiving rVWF, the index date was the date on which rVWF prophylaxis was first initiated. For patients receiving pdVWF, the index date was the date of initiation of the most recent prophylactic treatment with a pdVWF agent. Patient data including demographics, clinical characteristics, treatment history, and clinical outcomes were extracted from medical records by study site investigators for the 6 months prior to the index date (pre-index period) and throughout the post-index period, defined as the period from the index date to treatment discontinuation, end of data availability, or death, whichever occurred first. Ethics approval and informed consent were obtained where applicable. Results In total, 15 patients received rVWF prophylaxis (continuous, n=12; intermittent, n=3) and 12 patients received pdVWF prophylaxis (continuous, n=11; intermittent, n=1). For patients who received rVWF prophylaxis, the median (range) age at treatment initiation was 38.0 (23.1–82.8) years, 10 (66.7%) were female, and 8 (53.3%) had Type 3 VWD. The most common comorbidities at treatment initiation were anemia, joint arthropathy, and menorrhagia, each reported for 5 (33.3%) patients. Eleven (73.3%) patients had received pdVWF with factor VIII prophylaxis prior to initiating rVWF. The most common reasons for initiating continuous rVWF prophylaxis were switching from another treatment (n=9, 75.0%) and effectiveness (n=8, 66.7%). Effectiveness, caregiver preference, and patient preference were the reasons given for initiating intermittent rVWF prophylaxis for all three patients. Median (range) duration of continuous and intermittent rVWF prophylaxis was 43.2 (6.8–69.0) and 33.3 (14.7–35.0) months, respectively. During the 6-month pre-index period, the median (range) annual bleeding rate (ABR) was 2.0 (0.0–8.1) for all patients receiving rVWF prophylaxis. During the post-index period (median duration 35.0 months), the median (range) ABR was 0.5 (0.0–12.3). For patients who received pdVWF prophylaxis, the median (range) age at treatment initiation was 45.4 (28.2–64.0) years, 8 (66.7%) were female, and 5 (41.7%) had Type 3 VWD. The most common comorbidities at treatment initiation were anemia (n=7, 58.3%), iron deficiency (n=6, 50.0%), and gastrointestinal complications (n=5, 41.7%). Of the 11 patients who received continuous pdVWF prophylaxis, 7 (63.6%) received Wilfactin/Willfact, 3 (27.3%) received Voncento, and 1 (9.1%) received Wilate/Eqwilate. Haemate P was administered to the 1 patient who received intermittent pdVWF prophylaxis. Median (range) duration of continuous and intermittent pdVWF prophylaxis was 75.8 (6.6–165.5) and 18.1 (18.1–18.1) months, respectively. During the 6-month pre-index period, the median (range) ABR was 1.0 (0.0–128.4) for all patients receiving pdVWF prophylaxis. During the post-index period (median duration 66.0 months), the median (range) ABR was 0.4 (0.0–29.3). Conclusions This real-world study investigating the use of rVWF and pdVWF prophylaxis in clinical practice in Europe highlights the effectiveness of rVWF prophylaxis in patients with VWD. Further research involving a larger sample of patients is warranted to enable comparisons between rVWF and pdVWF prophylaxis.