Prophylaxis with Once, Twice or Three-Times Weekly Dosing of rFVIII-FS prevents Joint Bleeds in a Previously Treated Pediatric Population with Moderate/Severe Hemophilia A

Introduction

Hemophilia A is classified as a mild, moderate or severe bleeding disorder based on circulating coagulation factor FVIII levels of 0.05 IU/mL (>5%), 0.01 to 0.05 IU/mL (1–5%), and 0.01 IU/mL (<1%), respectively.1, 2 Recurrent bleeding episodes into the joints, typically beginning from an early age in life (children aged 1–2 years), are the hallmark of severe hemophilia,3, 4 and a proportion among moderate hemophilia population are affected.5 Joint bleeds (hemarthroses) often occur spontaneously or with minimal or unknown trauma. Repeated bleeding events into a joint lead to progressive joint damage (hemophilic arthropathy), debilitating dysfunction, chronic pain, and reduced health related quality of life (HRQoL).3, 6 Compared to patients with moderate/mild hemophilia and to non-hemophiliacs, individuals with severe hemophilia have statistically lower levels of HRQoL.6

Abstract

PURPOSE

This prospective study evaluated three different prophylaxis regimens for preventing joint bleeds and preserving the joint status in previously treated children with severe or moderate hemophilia A.

METHODS

Previously treated children (>20 exposure days [ED], on-demand or prophylaxis) with severe or moderate hemophilia A were allocated to receive one of three treatment regimens – regimen 1: subjects received 70 IU/kg once per week; regimen 2: subjects received two doses per week (30 IU/kg plus 40 IU/kg); and regimen 3: subjects received 25 IU/kg three times per week; with option for escalation for regimen 1 and 2 in the event of a joint bleed. The primary efficacy variable was the proportion of patients with <2 joint bleeds during the 9-month treatment period.

RESULTS

A total of 32 children, aged between 1 and 13 years, participated in this study, and all of them were included in the efficacy and safety analysis. Overall, 78.1% of subjects achieved the primary efficacy endpoint. All three regimens reduced the bleeding rate compared to 6 months prior to study entry. This was accompanied by a stabilized or even improving joint status and an improved quality of life. Dose escalation was required in seven patients. All regimens were well tolerated, and the incidence of adverse events (AEs) during the study period was as expected for children in this age group. One case of transient low titer FVIII inhibitor development in a previously untreated child was reported. The results indicated a higher effectiveness of regimen 3.

CONCLUSION

This study demonstrated that prophylaxis with once, twice, and especially three-times weekly rFVIII-FS dosing protects children from bleeding events, in particular from joint bleeds.

Keywords

recombinant factor VIII, FVIII, prophylaxis in children, hemophilia A, arthropathy, hemarthroses, joint bleeds