The Australian experience with switching to extended half‐life factor VIII and IX concentrates: On behalf of the Australian Haemophilia Centre Directors' Organisation

Abstract

Introduction Extended half‐life (EHL) factor (F) VIII and FIX concentrates became available to selected haemophilia A (HA) and haemophilia B (HB) patients in Australia in March 2018. Aim To determine factor utilization and bleeding outcomes during the first 6 months of prophylaxis with EHL concentrates, and compare it to the last 6 months of prophylaxis with standard half‐life (SHL) concentrates. Methods A national, retrospective study was performed using data extracted from the Australian Bleeding Disorders Registry (ABDR). Patients with ≥3 months of EHL exposure were analysed. Results A total of 129 HA patients (86 Adynovate, 43 Eloctate) and 64 HB (Alprolix) patients were included in the study. For HA, switching to EHL FVIII resulted in decreased injection frequency (3 to 2 per week), improved ‘reduced adherence’ rates (18% to 7%), decreased median annualized bleeding rate (ABR; 2.0 to 0.0) and increased proportion of patients with zero bleeds (44% to 64%). Actual factor utilization increased by 20 IU/kg/wk on Adynovate and 4 IU/kg/wk on Eloctate. For HB, switching to EHL FIX resulted in decreased injection frequency (2 to 1 per week), improved ‘reduced adherence’ rates (35% to 11%), decreased median ABR (3.0 to 2.0) and increased proportion of patients with zero bleeds (31% to 46%). Actual factor utilization decreased by 4 IU/kg/wk. There was no clinically significant inhibitor development. Conclusion Compared to SHL, EHL FVIII resulted in improved bleeding outcomes, albeit at the expense of increased factor utilization. EHL FIX resulted in improved bleeding outcomes despite decreased factor utilization.

Bleeding outcomes and factor utilization after switching to an extended half-life product for prophylaxis in haemophilia A in Austria

“…However, we found no statistically significant change in factor usage and costs, in contrast to other real-world data, indicating that a decrease in factor consumption is possible 14 , 17 – 19 , 26 . The difference in our findings could be explained by the low-dose prophylactic regimen for SHL in Austria 27 .…”

“…The switch to the EHL has met the expectations based on the primary reasons for switching, as we observed a statistically significant reduction in ABR and prophylactic infusion frequency per week after switching from SHL to EHL. This was also found in other publications from high-income countries investigating rFVIII-Fc, reporting higher trough levels, lower infusion frequencies and improved bleeding outcomes 6 , 17 – 19 , 26 .…”

Real‐world outcomes with recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis: Longitudinal follow‐up in a national adult cohort

“…Other real-world studies have demonstrated a reduction in factor consumption with rFIXFc prophylaxis. 17,19,20 This study also demonstrated that rFIXFc was effective in the management of bleeds in the acute setting. One or two infusions of rFIXFc resolved 90% of acute bleeds, which is similar to that reported in the phase 3 clinical trial where 97% of bleeding episodes resolved with one or two infusions.…”

“…9 Similar ABRs have been reported in other real-world studies. 17,18,20 This improvement is multifactorial, influenced by higher trough levels achieved with rFIXFc prophylaxis and more PWSHB able to achieve effective prophylaxis. The longer prophylaxis intervals possible with rFIXFc enabled patients to consider prophylaxis who were previously only able to access episodic treatment with SHL rFIX, primarily due to poor venous access, fulfilling one of the expectations of EHL products.…”

“…Onceweekly rFIXFc prophylaxis (dose 50 IU/kg) was associated with an annualised bleeding rate (ABR) of 2, and 46% participants reported an ABR of 0. 17 The use of lower weekly doses of rFIXFc prophylaxis (30 IU/kg) in a small cohort of PWSHB has reported median trough levels of 0.04 IU/ml and ABR of 4. 18 Treatment with EHL-FIX products has also demonstrated nearly 50% reduction in factor consumption compared with SHL factors.…”