A Pooled Analysis of Treatment with a Plasma-Derived von Willebrand Factor (VWF) Almost Devoid of Factor VIII in Paediatric Patients with Von Willebrand Disease (VWD)

Introduction Von Willebrand factor (VWF) replacement therapy is commonly used in the treatment of patients with von Willebrand Disease (VWD) who do not respond to or cannot use desmopressin. While its effectiveness in adults is well-known, it is important to investigate its usage in the paediatric population, as it is a key element in the clinical trial programme of a VWF product because children may respond differently to treatment.

Method This pooled analysis gives new data from five clinical studies conducted by LFB between 1999 and 2014, using a plasma-derived VWF concentrate almost devoid of factor VIII (FVIII) in patients under 18 years old. A total of 56 paediatric patients were included in the analysis, categorised into three age groups (<6 years, 6-11 years, and 12-<18 years). These patients received at least one injection of VWF for the treatment of bleeding episodes (BE), prevention during surgery, as well as short or long-term prophylaxis to prevent BE.

Results Among the patient population, 54% were female. Most patients had type 3 (25) or type 2 (27) VWD. Basal FVIII:C (factor VIII coagulant activity) levels were<20 IU/dL in 59% of patients. The treatment efficacy and safety were assessed based on 122 BEs (including gastrointestinal, musculoskeletal, epistaxis, intrabuccal, and other types) and 29 surgical/invasive procedures (including orthopaedic, urological, dental, and general procedures). Investigator assessment of treatment was rated as excellent/good in 89.3% of BEs and 100% of surgical/invasive procedures. The dosages of VWF varied between age groups and specific clinical situations. FVIII was co-administered in 23% of treatment events. Long-term prophylaxis was given for 22 occasions in 17 patients, approximately twice a week with a median dose of 40 IU/kg (patients aged≥12 years) and 50 IU/kg (other age groups). Adverse drug reactions were reported in only one 17-year-old patient (1.8%), consisting of two non-serious episodes of dizziness that resolved within 15 minutes without any corrective treatment. No inhibitors were reported in any of the trials.

Conclusion This data suggests that a plasma-derived VWF concentrate with low FVIII content, is effective and has a favourable safety profile in paediatric patients with VWD. Similar to adults, the dosage and duration of treatment should be adjusted based on the patient's clinical condition and VWF:RCo (VWF Ristocetin cofactor) and FVIII:C plasma levels during treatment.

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Artikel online veröffentlicht:
26. Februar 2024