HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

No abstract

No abstract

International guidelines conditionally recommend long-term prophylaxis in patients with von Willebrand disease (VWD) and severe/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. Planned duration of rVWF prophylaxis was 12 months; starting rVWF dose was 50±10 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 of treated spontaneous BEs (sABR) during rVWF prophylaxis. Over the 12-month study period, treated sABR decreased by 91.5% on-study versus historical sABR in 13 patients in Prior On-Demand group, and by 45.0% in 10 patients in Switch group (model-based analysis ratio [95% CI]: 0.085 [0.021-0.346] and 0.550 [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. Trial registration: www.clinicaltrials.gov (#NCT02973087) and www.clinicaltrialsregister.eu (#EudraCT 2016-001478-14).

Ongoing institutional and cooperative group efforts to minimize radiation exposure are justified given the high rate of serious toxicity observed in our long-term survivors. Follow-up through long-term multidisciplinary clinics is important and warranted for all patients exposed to radiotherapy in childhood.