Secondary Prophylaxis with rFVIIa Improves Quality of Life of Hemophilia Patients with Inhibitors and Frequent Bleeds.
Authors: Konkle Barbara A. , Ebbesen Liselotte S. , Auerswald Guenter K.H. , Friedrich Ute , Ljung Rolf C.R. , Roberts Harold R. , Hoots W. Keith 
Published: April 2020

Abstract
Introduction: Patients with hemophilia and neutralizing antibodies (inhibitors) against exogenous factor VIII or factor IX characteristically have impaired joint function and more hospitalizations compared with those without inhibitors. We investigated the impact of secondary prophylaxis with activated recombinant factor VII (rFVIIa) on quality of life (QoL) and health-related quality of life (HRQL) in patients with congenital hemophilia A or B with inhibitors and high requirements for on-demand therapy.
Methods: In a prospective, randomized, double-blind, uncontrolled trial, 22 patients (inhibitor titer &gt;2 BU/mL; and ≥4 bleeds/month) received secondary prophylaxis with rFVIIa (90 or 270 μg/kg) once daily. This was preceded by a 3-month observation (baseline) period and followed by a 3-month post-treatment follow-up period in which patients were treated on-demand for their bleeds. QoL was evaluated by hospitalizations related to bleeds, days unable to attend/absence from school or work, or days requiring mobility aids. HRQL was assessed with the EuroQoL (EQ-5D), a 5-dimensional measure of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 3 levels (no problem; some or moderate problems; and extreme problems/impossible to do).
Results: The clinically relevant reductions in bleed frequency observed with rFVIIa 90 or 270 μg/kg during prophylaxis (45% and 59%; p&lt;0.0001 for both) compared with on-demand therapy during the observation period (baseline) were maintained during the 3-month follow-up period and were associated with improvements in QoL. The proportion of days during prophylaxis where patients were unable to attend/absent from school/work was significantly less than at baseline (16.7% vs 38.7%; p=0.0127, in a post-hoc analysis of the two treatment arms combined) and a significantly lower percentage of days was spent in hospital (5.9% vs 13.5%; p=0.0026 [post-hoc analysis]). During the post-treatment period, there were non-significant trends towards this effect being maintained (28.1% days absent from school/work, and 10.3% days spent in hospital). Overall use of mobility aids during prophylaxis and during the post-treatment period remained unchanged from that at baseline (post-hoc analysis). With EQ-5D, 2 of the measures (pain and mobility) showed trends towards improvement over time. Fewer patients tended to have pain and mobility problems during prophylaxis and during the post-treatment period.
Conclusion: Prior to entry, patients enrolled in this trial bled frequently and overall had significant joint disease. Clinically relevant reductions in the number of bleeds observed during prophylaxis with rFVIIa compared with conventional on-demand therapy were associated with considerable improvements in QoL, reflected in a variety of important measures. Our results support the concept that secondary prophylaxis with rFVIIa in patients with severe hemophilia A or B with inhibitors and frequent bleeds improves the QoL of these disabled patients.