PB0679 - Local experience of monitoring and effectiveness of Emicizumab in severe Haemophilia A

Background: Development of Emicizumab (Hemlibra) a bispecific monoclonal antibody that substitutes for activated factor VIII by directly binding activated FIX to FX, initially for haemophilia A patients with inhibitors, it is now a treatment option for all severe haemophilia A patients, bringing potential for improved clinical outcomes and quality of life.

Aims: To assess stability of circulating levels of Emicizumab and clinical effectiveness of prophylactic treatment in bleed prevention in local cohort of severe haemophilia A patients without inhibitors.

Methods: Citrated plasma samples were collected from 19 severe haemophilia A patients on Emicizumab having commenced maintenance dose at week 5 then 3, 6, 9 and 12 months as part of routine care, 7 patients with complete time points. Dosing was fortnightly, according to manufacturer’s recommendations. Emicizumab levels were measured using a specific one-stage assay with R2 Diagnostic calibrators and controls, performed on STAR MAX2 (Stago). Thrombin generation using CAT analyser (Thermo) and Thrombinoscope reagents was measured at week 5. ANOVA and descriptive statistics were applied.

Results: Circulating levels of Emicizumab for all patients mean = 50.5ug/mL, median = 50.4ug/mL, with no statistically significant difference p = 0.924 across time points (see Table 1). Comparison between individual patients range 22.2– 66.7ug/mL showed statistically significant difference p = < 0.001. Endogenous thrombin potential (ETP) mean = 1225.7nM/mins and Peak thrombin mean = 117.9nM with 92.3% and 23.1% respectively within normal range. There was no correlation between Emicizumab level and ETP or Peak thrombin R2 = 0.03, 0.16 respectively. There were 6 spontaneous bleeds recorded with 66.6% in patients with levels < 50ug/mL.

Conclusion(s): Local experience of self-administered Emizicumab, treatment showed good circulating stability in all haemophilia A patients consistent with trial findings. Results support 50ug/mL threshold but in the future, perhaps dose adjustment could be used with monitoring to guide optimise clinical effectiveness and minimise bleeds.