Effectiveness of long‐term prophylaxis using pdFVIII/VWF concentrate in patients with inherited von Willebrand disease

Abstract

Background Patients with symptomatic von Willebrand disease (VWD) should be offered long‐term prophylaxis (LTP) to prevent recurrent bleedings. Our objective was to evaluate the effectiveness and safety of Voncento®, a plasma‐derived FVIII/VWF concentrate (ratio 1:2.4), administrated in LTP. Methods We included patients from the OPALE study (May 2016 to April 2021), a French multicenter observational study following patients with inherited VWD, who received a Voncento® LTP during the study period. Results Among the 130 OPALE‐study patients, 23 patients (12 women) received a LTP and were therefore included. The median (range) age was 16 (1–85) years; 16 patients were type 3, 1 was type 2A, 6 were type 2B. Before inclusion, 19 (83%) were under LTP and 4 (17%) received on‐demand (OD) treatment. The indications for initiating prophylaxis in the overall population were joint bleeding (43%), ear, nose, and throat (ENT) bleeding including epistaxis or oral bleeding (39%), and recurrent muscle hematoma (22%). The medians (ranges) dose of Voncento® per infusion, frequency, and weekly dose were 45 (33–109) IU/kg, 2 infusions per week, and 96 (44–222) IU/kg/week, respectively. The median (range) annualized bleeding rate (ABR) was 0.8, 0.7 (0–3.5), and 0 (0–2.3) for type 2A, 2B, 3 patients, respectively. There was no difference regarding to the dose, frequency of infusion, or in terms of ABR in 9/19 patients who replaced previous concentrates with Voncento®. During the study period, no adverse event was reported. Conclusion These results suggest that Voncento® is effective to prevent recurrent bleedings in patients symptomatic VWD.

A Systematic Review of Efficacy and Safety of Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Voncento) in von Willebrand Disease

“…Eight studies evaluated the efficacy of pdVWF/FVIII for LTP treatment (Table 2). Prophylactic efficacy was reported as excellent/good in 98-100% of patients in four publications, 10,14,15 and 89% of patients in a fifth (Table 2). 18 The OPALE study reported hemostatic efficacy according to VWD type, where excellent/good effectiveness was reported in 100% of patients (N=23) with types 2A (N=1), 2B (N=5), and 3 (N=16) where these data were available.…”

“…18 The OPALE study reported hemostatic efficacy according to VWD type, where excellent/good effectiveness was reported in 100% of patients (N=23) with types 2A (N=1), 2B (N=5), and 3 (N=16) where these data were available. 14 Pooled hemostatic efficacy scores for treatment of breakthrough bleeds were pooled from 252 treated bleeds from 37 patients across nine studies (Figure 2B), where 96% of bleeds (N=242) were resolved with excellent/good efficacy and 4% (N=10) had moderate efficacy. 6,[8][9][10][13][14][15][16]18 Three studies reported consumption data for pdVWF/FVIII for LTP treatment, 6,10,11 and LTP regimen were reported in 6 of 8 studies reporting LTP outcomes.…”

“…14 Pooled hemostatic efficacy scores for treatment of breakthrough bleeds were pooled from 252 treated bleeds from 37 patients across nine studies (Figure 2B), where 96% of bleeds (N=242) were resolved with excellent/good efficacy and 4% (N=10) had moderate efficacy. 6,[8][9][10][13][14][15][16]18 Three studies reported consumption data for pdVWF/FVIII for LTP treatment, 6,10,11 and LTP regimen were reported in 6 of 8 studies reporting LTP outcomes. 6,[8][9][10]14,18 Dosing was reported as mean VWF:RCo IU per infusion, weekly dose and median dose to treat NSB events (Supplemental Table 8).…”

HRQoL and psychosocial aspects of burden on caregivers to children with moderate or severe von Willebrand disease

“…Prophylactic treatment with factor concentrates is standard care for children with more severe bleeding phenotypes in high-income countries. 5 Caregivers are highly involved in the advanced treatment of the disorder. From the time of the child's bleeding diagnosis caregivers face new demands, such as recognition and evaluation of bleeds, treatment options, frequent hospital visits and uncertainty about the future.…”

“…The aim of treatment is to stop an ongoing bleed and to prevent bleeding, and thereby enable daily life and participation in physical activities. Prophylactic treatment with factor concentrates is standard care for children with more severe bleeding phenotypes in high‐income countries 5 . Caregivers are highly involved in the advanced treatment of the disorder.…”