Patient/Caregiver‐reported recombinant factor VIIa (rFVIIa) dosing: home treatment of acute bleeds in the Dosing Observational Study in Hemophilia (DOSE)

Abstract

Patients with congenital haemophilia with inhibitors experience acute bleeds managed with bypassing agents, such as recombinant FVIIa (rFVIIa). Home-based treatment and dosing patterns in the US remain poorly described. This study aimed to assess the prescribed and actual rFVIIa dosing in frequently bleeding inhibitor patients (≥4 bleeds in 3 months) prescribed first-line therapy with rFVIIa. Patients or caregivers recorded daily diaries, including the details of all bypassing agent infusions for 3-6 months. Median (range) initial rFVIIa dose prescribed for joint, muscle and other bleeds was 167.5 (61.0-289.0) mcg kg(-1). Additional rFVIIa doses prescribed were 90 (61-270) mcg kg(-1) at an interval of 2.5-3 (1-24) h. The actual initial rFVIIa dose reported by patients/caregivers for 158 bleeds was 212 (59-400) mcg kg(-1), with total dose per episode of 695 (74-21257) mcg kg(-1). Patient/caregiver-reported average dose per bleed was 146 (40-400) mcg kg(-1) across 5 (1-106) infusions. The initial rFVIIa dose was higher for haemarthrosis (223 [59-400] mcg kg(-1)) than muscle bleeds (148 [74-300] mcg kg(-1); P = 0.07). Initial and mean dose per day changed as treatment progressed. The DOSE study indicates that frequently bleeding inhibitor patients are prescribed and use higher rFVIIa dosing for all bleed types than recommended in the package insert (90 mcg kg(-1)). The rFVIIa dosing was highly variable within and across bleed types, with higher initial doses used for joint bleeds than muscle and other bleed types, particularly in the first days of treatment. This suggests that patients/caregivers have adopted home treatment strategies based on physician discretion and individual responses and experience.

Impact of Acute Bleeding on Daily Activities of Patients with Congenital Hemophilia with Inhibitors and Their Caregivers and Families: Observations from the Dosing Observational Study in Hemophilia (DOSE)

“…Its detailed methodology has been described elsewhere [7], and the primary end point was characterization of treatment of bleeding episodes [8]. HRQOL, burden of illness, and loss of workdays or school days were evaluated as planned secondary end points [9].…”

“…Patients' demographic characteristics and history have been published previously [7][8][9][10]. Of 52 patients enrolled, 39 completed daily diaries (or had diaries completed for them by their caregivers); the majority had hemophilia A (85%) and were white (69%).…”

“…Of 52 patients enrolled, 39 completed daily diaries (or had diaries completed for them by their caregivers); the majority had hemophilia A (85%) and were white (69%). Thirty-seven participants reported using rFVIIa as ondemand-only treatment, 5 were also on immune tolerance therapy, and 12 reported receiving routine prophylaxis with BPAs to prevent bleeding [8][9][10]. For diary completers, the median (range) age was 16.2 (1.6-60.9) years [8], with 31% being younger than 11 years and 23% aged 11 to 18 years [7,8].…”

“…Thirty-seven participants reported using rFVIIa as ondemand-only treatment, 5 were also on immune tolerance therapy, and 12 reported receiving routine prophylaxis with BPAs to prevent bleeding [8][9][10]. For diary completers, the median (range) age was 16.2 (1.6-60.9) years [8], with 31% being younger than 11 years and 23% aged 11 to 18 years [7,8]. Participants reported a median of 13 bleeding episodes within the previous year [8,9].…”

“…Dosing Observational Study in Hemophilia (DOSE) was a prospective, multicenter, noninterventional, and observational diary study designed to examine the use of BPAs-and specifically rFVIIa-in the home setting [7]; it also evaluated the correlation of prescribed and actual dosing [8] as well as daily assessments of health-related quality of life (HRQOL) [9]. DOSE also evaluated the impact of bleeding episodes on patient and caregiver daily activities, absenteeism, and productivity.…”