Key Drivers of Coagulation Factor Use in Von Willebrand Disease During Hospitalization: An Overview of the French BERHLINGO Cohort.

BACKGROUND: Von Willebrand disease (VWD) is the most common inherited bleeding disorder. However, studies of hospitalisation patterns with replacement treatment are scarce. OBJECTIVES: The aim of this study was to investigate the current therapeutic management of VWD and determine the key drivers of coagulation factor uses in patients during hospitalisation. METHODS: Hopscotch-WILL was a multi-centric retrospective study conducted over a 48-month period in any patients with VWD. The data were collected from the BERHLINGO Research Database and the French Hospital database. RESULTS: A total of 988 patients were included; 153 patients (15%) were hospitalised during 293 stays requiring treatment with von Willebrand factor (VWF) concentrates-pure or in association with Factor VIII (FVIII). Their median basal concentrations of VWF and FVIII were significantly lower than in untreated patients: VWF antigen < 30 IU/dL, VWF activity < 20 IU/dL and FVIII:C < 40 IU/dL. The median (interquartile range) concentrate consumption was similar between highly purified VWF or VWF combined with FVIII (72 [110] vs 57 [89] IU/kg/stay, p = 0.154). The use of VWF was highly heterogeneous by VWD type; type 3 had a particularly high impact on VWF consumption in non-surgical situations. The main admissions were for ear/nose/throat, hepato-gastroenterology, and trauma/orthopaedic conditions, besides gynaecological-obstetric causes in women. CONCLUSIONS: The use of VWF concentrates is mostly influenced by low basal levels of VWF and FVIII, but also by VWD type or the cause for hospitalisation. These results could inform future studies of newly released recombinant VWF.

Efficacy and safety of turoctocog alfa in patients with hemophilia A requiring surgical procedures: A multicentre retrospective study.

BACKGROUND: Turoctocog alfa is a recombinant Factor VIII used in patients with hemophilia A. The aim is to assess the real-life evidence of turoctocog alfa in surgery. STUDY DESIGN AND METHODS: Data were extracted from a national database. RESULTS: Turoctocog alfa was used for 86 surgeries (49 major and 37 minor) in 56 patients. The results are expressed as medians (interquartile range). Six (10.7%) patients had severe hemophilia A, four (7.1%) moderate, and 46 (82.2%) mild. For patients who underwent major surgeries, basal plasma FVIII coagulant activity (FVIII:C) levels were 15 IU.dL-1 (8-22). Eight (5-14) infusions were given, at a preoperative loading dose of 40.0 (35.0-45.5) IU.kg-1 and a total dose of 253.3 (125.0-507.0) IU.kg-1 . In patients who underwent minor surgeries, basal FVIII:C levels were 18 IU.dL-1 (9-31). Two (1-3) infusions were required, at a preoperative loading dose of 34.0 (28.8-38.5) IU.kg-1 and a total dose of 73.7 (37.6-122.1) IU.kg-1 . The overall clinical efficacy was judged excellent/good in 77 procedures (89.5%) and fair/poor in nine (10.5%). The fair/poor efficacy concerned seven patients (six mild hemophilia and one severe), for four urological surgeries, two dermatological procedures, one heart surgery, one ear-nose-throat procedure, and one dental avulsion in the patient with severe hemophilia. Three out of those seven patients received antiplatelet therapy. No thromboembolic events, anti-FVIII antibodies, or adverse events were reported. DISCUSSION: The efficacy and safety of turoctocog alfa were confirmed for the management of surgery in patients with hemophilia A. No adverse events were observed and overall efficacy was good.

rFVIII-Fc in severe haemophilia A: The incentive switch in case of high risk of joint bleedings.

BACKGROUND: Efmoroctocog alfa, the first recombinant factor VIII fusion protein with extended half-life (rFVIII-Fc), has been hypothesized to lower FVIII consumption in patients with severe Haemophilia A (pwSHA), without reducing clinical efficacy. What about real life? METHOD: MOTHIF-II was a noninterventional, multicentre, before/after study, via the collection of retrospective data from July 2015 to June 2016 (called T1), and from July 2017 to June 2018 (called T2), in 7 French haemophilia treatment centres. We examined the prescriptions and dispensations of factor VIII and the Annual Bleeding Rate (ABR), in pwSHA without current inhibitors on prophylaxis, before and after the introduction of rFVIII-Fc. The data gathered from the BERHLINGO research database and from the French Healthcare claims database with a determinist pairing process based on the national unique identification number. RESULTS: A total of 156 pwSHA were included in the prescription cohort and 83 in the ABR cohort. For switched patients, the mean amounts of prescribed FVIII were significantly higher during T1 compared to T2 (4333 (2052) vs. 3921 (2029) IU/kg/year/patient, p: 0.028); a significant decrease in their ABR was also observed between T1 and T2 (6.3 (6.0) vs. 4.4 (5.4), p: 0.047). These patients had a more severe bleeding profile centred on haemarthrosis. CONCLUSION: The results are related to those of the pivotal clinical trials for the reduction in FVIII consumption following the switch to rFVIII-Fc, with a significant improvement in the haemorrhagic phenotype for pwSHA.

Bleeding complications during pregnancy and delivery in haemophilia carriers and their neonates in Western France: An observational study.

BACKGROUND: Pregnancy, delivery and the postpartum period expose haemophilia carriers, as well as their potentially affected neonates to a high risk of haemorrhagic complications. OBJECTIVES: To describe bleeding complications in haemophilia carriers and their newborns throughout pregnancy and postpartum and to identify potential factors increasing the risk of bleeding in this population. PATIENTS/METHODS: The ECHANGE multicentre observational cohort study was conducted between January 2014 and February 2019 using the BERHLINGO database comprised of patients from seven French haemophilia centres. RESULTS: During the 5 years study period, a total of 104 haemophilia carriers and 119 neonates were included, representing 124 pregnancies and 117 deliveries. Thirty-five (30%) bleeding events were observed, most of them (83%) occurred during the postpartum period, and 37% were reported during the secondary postpartum. Neuraxial anaesthesia was not complicated by spinal haematoma. Three (2.5%) neonates experienced cerebral bleeding. Caesarean section was associated with an increased risk of maternal bleeding in primary and secondary postpartum periods. Basal factor level <0.4 IU/mL was also found to be associated with an increased risk of bleeding during secondary postpartum. CONCLUSION: In our cohort, bleeding events occurred in more than a third of haemophilia carriers mainly in the postpartum period, and a significant portion of this bleeding occurred during the secondary postpartum. Haemophilia carriers warrant specific attention during primary and secondary postpartum, in particular in case of caesarean section and low basal factor level. The ECHANGE study is registered at clinicaltrials.gov identifier: NCT03360149.

Cost of home and hospital care for patients with cystic fibrosis followed up in two reference medical centers in France.

OBJECTIVES: In France, new guidelines for clinical practices concerning cystic fibrosis came out in 2002, underscoring the need for early and intensive management of this disease. Because no recent health economic studies on cystic fibrosis in France were available, we conducted a cost-analysis study before the new guidelines were put into practice, with a view to a later study on the medical and economic impact of these guidelines. METHODS: A cost-analysis study was performed of the inpatient and outpatient costs of patients with cystic fibrosis for the 2000-2001 period. The various direct costs were estimated on a sample of sixty-five adult and pediatric patients managed for cystic fibrosis in two reference medical centers. Data were obtained from medical records, and questionnaires were filled out by the patients. Analysis was made from the perspective of the French healthcare system. RESULTS: We studied sixty-five patients, 54 percent male patients and 72 percent children under 18 years of age. The total cost of cystic fibrosis care totaled 16,189 euros per year and per patient. Outpatient costs accounted for 88 percent of the total cost versus 12 percent for inpatient costs; medication costs were the highest with 21 percent of the total cost for home intravenous antibiotic treatments and 49 percent of the total cost for chronic medications. CONCLUSIONS: The results show that outpatient costs were higher than inpatient costs, which could be related to the importance granted to home health care in France, notably for intravenous antibiotic treatments given for pulmonary complications.