Switching to extended half-life factor VIII concentrates or non-factor replacement therapies in patients with severe-to-moderate haemophilia A without inhibition: retrospective analysis. Experience of the Galician Thrombosis and Hemostasis Working Group (G2TH-AGHH)

Introduction: The concept of prophylaxis in hemophilia has changed significantly due to the shift from standard half-life (SHL) to extended half-life (EHL) factor VIII concentrates and the emergence of the subcutaneous administration of emicizumab. Objective: To report the experience and results of prophylaxis in patients with moderate-to-severe hemophilia A in Galicia, Spain after switching from SHL-CF8 to EHL-CF8 or emicizumab. Methods: Retrospective study of patients with severe-to-moderate hemophilia A without inhibition who switched from SHL-CF8 to EHL-CF8 or emicizumab in Galicia until December 2023. The analysis covers the 12 months prior and 12 months following the switch, and the last 12 months after the switch. Data were collected from patients’ electronic health records. Results: a total of 27 men were included, with a median age of 29.5 years (range, 5-57) and prior SHL-CF8 prophylaxis. Median F8 consumption changed from 312,000 IU/year for SHL-CF8 to 266,875 IU/year for EHL-CF8, with a decrease in the median number of weekly infusions from 3 down to 1.875 and an increase in the trough F8:C level from 1.67 up to 3.8 IU/dL. The mean bleeds (annualized bleeding rate [ABR]) occurred in the period of SHL-CF8 use was 2.33, vs 0.83 with EHL-CF8, dropping down to 0.3 over the past 12 months (p < 0.0028 and p < 0.0002, respectively). The mean spontaneous ABR was 0.45, 0.33 and 0.1 respectively, and the joint ABR dropped from 1.66 down to to 0.66 and 0.13 after the switch. Arthropathy was described in 42.31% and 36.36% after the switch and over the past 12 months, respectively. In addition, 4 patients switched to emicizumab, with a reduction in the total mean number of ABR from 1.5 down to 0 and spontaneous ABR from 0.25 down to 0, while joint ABR did not change (0 to 0) regardless of the frequency of emicizumab prophylaxis. The main reasons for the switch were reduction in the number of infusions and prevention of bleeding (15.38% each). The HEAD-US (Hemophilia Early Arthropathy Detection with Ultrasound) evaluation was not performed because it was not implemented in all centers. Conclusions: Overall, the results show an improved clinical profile for the patients who switched to the EHL product and, as result, an increased minimum through level, with lower consumption of the factor and reduction of treatment burden, which is consistent with clinical trials and the real-workd experience reported by other groups.