{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T05:00:25Z","timestamp":1791608425399,"version":"4.3.4"},"reference-count":37,"publisher":"American Society of Hematology","issue":"2","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/legalcode"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 \u00b1 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).<\/jats:p>","DOI":"10.1182\/blood.2021014810","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T18:12:34Z","timestamp":1650391954000},"page":"89-98","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":45,"title":["Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5677-1371","authenticated-orcid":false,"given":"Frank W. G.","family":"Leebeek","sequence":"first","affiliation":[{"name":"1Department of Hematology, University Medical Center, Erasmus MC, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-9864","authenticated-orcid":false,"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"2Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy;"},{"name":"3Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2944-0240","authenticated-orcid":false,"given":"Miguel","family":"Escobar","sequence":"additional","affiliation":[{"name":"4University of Texas Health Science Center at Houston, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3600-8536","authenticated-orcid":false,"given":"Andreas","family":"Tiede","sequence":"additional","affiliation":[{"name":"5Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-1317","authenticated-orcid":false,"given":"Giancarlo","family":"Castaman","sequence":"additional","affiliation":[{"name":"6Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wang","sequence":"additional","affiliation":[{"name":"7Hemophilia and Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, CO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7331-4364","authenticated-orcid":false,"given":"Tung","family":"Wynn","sequence":"additional","affiliation":[{"name":"8Department of Pediatrics, University of Florida, Gainesville, FL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovanna","family":"Baptista","sequence":"additional","affiliation":[{"name":"9Takeda Development Center Americas, Inc., Lexington, MA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0733-5551","authenticated-orcid":false,"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"10Takeda Development Center Americas, Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"10Takeda Development Center Americas, Inc, Cambridge, 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