Improvement in health‐related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study

Abstract

Little is known about the health-related quality of life (HRQoL) burden of haemophilia B. The aim of this study was to assess HRQoL burden of haemophilia B, the benefit of recombinant factor IX (rFIX) prophylaxis and the HRQoL benefit of achieving a zero annual bleed rate. Subjects receiving rFIX (BAX326) prophylaxis or on-demand completed the SF-36 survey. Baseline SF-36 scores were compared to the general US population scores to understand the HRQoL burden. Changes in SF-36 scores between baseline and follow-up were tested using t-tests. Subgroup analysis was conducted to examine SF-36 change among subjects who switched to BAX326 prophylaxis. SF-36 scores were also compared between those with zero bleeds and those who bled during the study. Compared to the US norms, subjects reported lower average scores in all physical and several mental HRQoL domains. At follow-up, prophylaxis subjects reported statistically significant and clinically meaningful improvements in overall physical HRQoL, as measured by the Physical Component Score (PCS) (mean change 2.60, P = 0.019), Bodily Pain (BP) (3.45, P = 0.015) and Role Physical (RP) domains (3.47, P = 0.016). Subjects who switched to prophylaxis from intermittent prophylaxis or on-demand experienced more pronounced improvements not only in the PCS (3.21, P = 0.014), BP (3.71, P = 0.026), RP (4.43, P = 0.008) but also in Vitality (3.71, P = 0.04), Social Functioning (5.06, P = 0.002) and General Health domains (3.40, P = 0.009). Subjects achieving zero bleeds reported lower BP (P = 0.038). Prophylaxis with BAX326 significantly improved HRQoL in patients with moderately severe or severe haemophilia B by reducing bleeds.

BAX326 (RIXUBIS): a novel recombinant factor IX for the control and prevention of bleeding episodes in adults and children with hemophilia B

“…The study confirmed the PK equivalence of the 2 products based on area under the curve (AUC) of plasma concentration versus time from 0 to 72 hours (AUC 0-72h ) [Windyga et al 2014a]. Repeated PK analysis at the end of the 6-month study in the third part of the study confirmed the initial findings for BAX326.…”

“…The overall median annualized bleeding rate (ABR) during the 6 months of twice-weekly prophylaxis with BAX326 was 1.99 (range 0-23.4). The overall mean ABR (4.20 ± 5.75) was significantly lower (79% difference; p < 0.001) than that seen in a historic control group of 276 patients who had received on-demand treatment (rFIX or pdFIX) in 12 earlier studies (20.0 ± 39.4) [Windyga et al 2014a]. Of 249 reported bleeds in the pivotal study, 211 (84.7%) were controlled with 1-2 infusions.…”

“…The incremental recovery at maximum concentration (C max ) was measured as 0.87 ± 0.22 and the half-life was 26.70 ± 9.55 hours, and 0.95 ± 0.25 IU/dl:IU/kg in the initial and final PK analyses. Moreover, the incremental recovery of BAX326 30 minutes postinfusion was consistent over time, suggesting no formation of subclinical inhibitors [Windyga et al 2014a]. …”

“…In total, 73 patients from 14 countries were enrolled into the full analysis set, of whom 59 received prophylaxis and 14 received ondemand treatment during the prophylaxis/treatment phase. At screening, most patients had arthropathy (88%) and target joints (66%), and only 18% were receiving consistent routing prophylaxis before the study [Windyga et al 2014a]. A historic control group was generated by meta-analysis of 12 previously published studies.…”

“…Of 249 reported bleeds in the pivotal study, 211 (84.7%) were controlled with 1-2 infusions. Hemostatic efficacy at bleed resolution was rated 'excellent' or 'good' in 96% of all bleeds (Figure 3) [Windyga et al 2014a].…”