Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
14 07 2022
14 07 2022
Historique:
received:
16
11
2021
accepted:
05
04
2022
pubmed:
20
4
2022
medline:
19
7
2022
entrez:
19
4
2022
Statut:
ppublish
Résumé
International guidelines conditionally recommend long-term prophylaxis in patients with von Willebrand disease (VWD) and severe and frequent bleeding. As recombinant von Willebrand factor (rVWF; vonicog alfa) may reduce the frequency of treated spontaneous bleeding events (BEs), we investigated the efficacy and safety of rVWF prophylaxis in adults with severe VWD. Patients with BEs requiring VWF therapy in the past year (on-demand VWF therapy [prior on-demand group] or plasma-derived VWF prophylaxis [pdVWF; switch group]) were enrolled in a prospective, open-label, nonrandomized, phase 3 study. The planned duration of rVWF prophylaxis was 12 months; starting rVWF dose was 50 ± 10 VWF: ristocetin cofactor (VWF:RCo) IU/kg twice weekly (prior on-demand group) or based on prior pdVWF weekly dose/dosing frequency (switch group). The primary endpoint was annualized bleeding rate (ABR) of treated spontaneous BEs (sABR) during rVWF prophylaxis. Over the 12-month study period, treated sABR decreased by 91.5% on-study vs historical sABR in 13 patients in the prior on-demand group, and by 45.0% in 10 patients in the switch group (model-based analysis ratio, 0.085; 95% confidence interval [CI], 0.021-0.346 and 0.550; 95% CI, 0.086-3.523, respectively). No treated spontaneous BEs were recorded in 84.6% (11/13) and 70.0% (7/10) of patients, respectively. The safety profile of rVWF was consistent with the previously established profile, with no new adverse drug reactions identified. Findings suggest that rVWF prophylaxis can reduce treated spontaneous BEs in patients previously receiving on-demand VWF therapy and maintains at least the same level of hemostatic control in patients who switch from prophylaxis with pdVWF to rVWF, with a favorable safety profile. This trial was registered at www.clinicaltrials.gov (#NCT02973087) and www.clinicaltrialsregister.eu (#EudraCT 2016-001478-14).
Identifiants
pubmed: 35439298
pii: S0006-4971(22)00545-6
doi: 10.1182/blood.2021014810
pmc: PMC9283967
doi:
Substances chimiques
Hemostatics
0
Recombinant Proteins
0
von Willebrand Factor
0
Banques de données
ClinicalTrials.gov
['NCT02973087']
Types de publication
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-98Informations de copyright
© 2022 by The American Society of Hematology.
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