Introduction and Objective:
Prospective clinical trials have demonstrated the efficacy of prophylaxis in reducing bleeding episodes in hemophilia A and B patients and those with inhibitors. However, data, predominantly from observational studies, have suggested more equivocal effects on health-related quality of life (HRQoL) [Buchbinder 2013]. The present review examined the impact of prophylaxis on HRQoL as measured during prospective trials.
Methods:
We conducted a systematic literature review of prospective studies evaluating the efficacy of prophylaxis in hemophilia using factor VIII, factor IX, or bypassing agents. Applying the inclusion criteria, we selected studies which evaluated HRQoL via validated instruments and summarized key data.
Results:
A total of 12 studies (hemophilia A [n=7]; hemophilia B [n=2]; inhibitors [n=3]) met all inclusion criteria and were reviewed. Of these studies, the investigational products were Advate (n=2), Kogenate (n=2), NovoEight (n=2), Eloctate (n=1), Rixubis (n=1), Aprolix (n=1), Feiba (n=2), and NovoSeven (n=1). HRQoL was assessed using one or a combination of the following instruments: SF-36 (n=3), EQ-5D (n=5), Haemo-QoL (n=2), Haem-A-QoL (n=3), Haemo-QOL-A (n=2) and general pain VAS (n=1). Seven of the 12 studies reported significant improvement in ≥1 HRQoL measure following prophylaxis. Advate, Rixubis and Feiba prophylaxis (among good responders with ≥ 50% bleed reduction) demonstrated statistically significant and clinically meaningful improvement in the physical component and certain domain(s) scores of the SF-36 (Valentino 2012; Windyga 2013; Gringeri 2013). Additionally, prophylaxis with Feiba showed clinically meaningful and/or statistically significant improvements in HRQoL (EQ-5D, Haemo-A-QoL), general health status (EQ-VAS) and general pain scores (VAS) (Antunes 2014; Stasyshyn 2014). Although, a previous Kogenate study indicated non-significant change in HRQoL measures (Collins 2003), recently published results from the SPINART trial demonstrated statistically significant and clinically meaningful improvement in several domains of the Haemo-QoL-A (Hong 2014). Prophylaxis with Eloctate and Alprolix resulted in non-significant change in the HRQoL measures used in their respective trials (Wyrwich 2013). Statistical and clinical significance were not reported for prophylaxis treatment with NovoEight (Santagostino 2014). Prophylaxis with NovoSeven showed a non-significant trend towards improvement in all dimensions of the EQ-5D but statistical improvement in general health status (EQ-VAS) (Hoots 2008).
Conclusion:
Results from Advate, Kogenate, Rixubis and Feiba trials offer robust evidence of clinically and statistically significant improvement in HRQoL in hemophilia patients treated with prophylaxis.