Low-Dose secondary prophylaxis May Decrease Haemorrhage and Improve Health-Related Quality of Life in Adults with Severe Hemophilia

Background and Introduction: A consensus of opinion exists among hemophilia doctors that the optimal management of patients with severe hemophilia during childhood is the administration of regular prophylactic infusions of factor concentrate. However, considering patient burden and costs, it is equally important to evaluate for how long prophylaxis is required. So we initiated a study to demonstrate the feasibility and benefits of the low-dose secondary prophylaxis for adults with severe hemophilia.

Methods: Patients with severe hemophilia A (F VIII < 1%) born between January, 1961, and January, 1988, who were treated at the hemophilia treatment centre at Nanfang hospital and treatment data available were eligible for enrollment in the study. The main exclusion criteria were a history of FVIII inhibitor (titer ≥ 0.6BU [Bethesda unit]), detectable FVIII inhibitors at screening (titer ≥ 0.4 BU), chronic liver disease, immunodeficiency, another hemostatic defect and the need for major surgery. An observational cohort study, using each patient as its own control, was conducted on adult patients with severe hemophilia switched from on-demand treatment to low dose secondary prophylaxis from January 2012 to December 2013. Enrollment began from December 2011 to January 2012. During the prophylaxis period, all participants received FVIII (including rFVIII Kogenate and pd FVIII Green Cross, Liaocheng, China) 10 IU kg^-1, twice a week. Breakthrough acute bleedings were treated according to the regular practice and guidelines. The study was approved by the Ethic Committee of Nanfang hospital, and informed consent was obtained from all patients before participation.

Results: The study was completed over a 2-year period (January 2012 to December 2013). Twenty adults with severe hemophilia performed on-demand treatment in preceding 5 years were enrolled. Switching to prophylaxis reduced the annual number of total and joint bleeds (median 24 vs. 8.5 and median 21 vs. 8.5; P < 0.001, respectively). The relative reduction in median annual number of total bleeds was 64.6% for subjects treated with prophylaxis compared with during on-demand treatment. Annual number of non-joint bleeds were also significantly lower (P < 0.001) on prophylaxis compared with during on-demand treatment (median 2 vs. 1 P < 0.001). After prophylaxis, the FISH score increased from median 22.5 (range 15-28) to median 24 (range 15-28) (P=0.016). Meanwhile, after two-years of prophylaxis, the number of target joints didn’t increase (median 8.5, range: 2-14; median 8.5, range: 2-14; P=0.317, respectively). The Health-related Quality of life (HRQoL) in patients with severe hemophilia were measured by the SF-36. The SF-36 score showed better results in terms of overall perceived health status between patients with On-demand period and with Prophylaxis period (P < 0.01) and all the seven domains like Physical Function, Role physical, Bodily Pain, General health, Vitality, Social function and Role emotional were improved after prophylaxis (P < 0.05), while Mental health did not differ significantly between the two groups (P=0.267).

Conclusion: The most important finding in this pilot study is its confirmation that low-dose secondary prophylaxis even in short-term does provide substantial benefits in controlling haemorrhage and improving daily activities/function, as well as improve HRQoL in China. Our study clearly established that low-dose prophylaxis can be provided efficiently for adults in a number of haemophilia treatment centers in China.