Blood Transfusion - 5 2019 (September-October)
A phase III study comparing secondary long-term prophylaxis versus on-demand treatment with vWF/FVIII concentrates in severe inherited von Willebrand disease
Authors:  Flora Peyvandi, Giancarlo Castaman, Paolo Gresele, Raimondo De Cristofaro, Piercarla Schinco, Antonella Bertomoro, Massino Morfini, Gabriella Gamba, Giovanni Barillari, Víctor Jiménez-Yuste, Cristoph Königs, Alfonso Iorio, Augusto B. Federici
Pages:  391-398
To cite this article:  Blood Transfus 2019; 17: 391-8
Doi:  10.2450/2019.0183-18
Published online:  04/02/2019

Background. There is a lack of prospective clinical trials specifically designed to evaluate the benefits of prophylaxis with vWF/FVIII concentrates in patients with inherited von Willebrand disease (vWD). The aim of the study was to compare efficacy of secondary long-term prophylaxis (PRO) with vWF/FVIII in the prevention of bleeding episodes in severe vWD patients to standard of care (on-demand treatment; ODT).
Materials and methods. In this 12-month, phase III, open-label study (PRO.WILL), vWD patients (aged ≥6 years) were randomised to PRO (n=9; 5 completed) or ODT (n=10; 7 completed) treatment with Fanhdi®/Alphanate® (Grifols) according to current licensing status for use in vWD. We assessed the proportion of patients who did not present any spontaneous bleeding episode, adverse events (AEs) or thrombotic events.
Results. All patients on ODT had vWD type 2 or 3 vs 70% of patients on PRO. All ODT patients experienced bleeds vs 60% on PRO. PRO patients showed fewer bleeds (n=32 vs n=172 [112 in the same patient, mostly mucosal]; p<0.0001) and lower risk of bleeding (relative attributable risk estimate: −0.667; 95% CI: −2.374, −0.107; p<0.001). Most frequent bleeds in ODT and PRO groups were, respectively, epistaxis (n=52 vs n=15) and gastrointestinal (n=13 [9 in the same patient] vs n=1). While most bleeds lasted one day under ODT (31/32), only epistaxis did so in PRO group (14/15). No AEs due to study medication were observed.
Discussion. Despite the small sample size and the heterogeneity of the study population, patients on vWF/FVIII prophylaxis showed a reduction in bleeding risk and rate compared to on-demand treatment.
Keywords: secondary long-term prophylaxis, on-demand treatment, von Willebrand disease, von Willebrand factor, factor VIII.
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