PB0519 - Does emicizumab prophylaxis lead to FVIII inhibitor reduction in hemophilia A patients with positive inhibitors?

Background: Prophylaxis with emicizumab significantly reduces bleeding events in persons with hemophilia A (PWHA) and positive inhibitors to FVIII. However, the influence of emicizumab on inhibitor titer remains to be elucidated.

Aims: The aim of this retrospective study was to demonstrate the influence of emicizumab prophylaxis on the titer of inhibitors to FVIII in PWHA and history of inhibitors.

Methods: PWHA and the history of inhibitors treated with emicizumab at the National Hemophilia Center were included in the study. The inhibitor titer was measured at two different time points, at the initiation of emicizumab prophylaxis (visit 1) and at the last visit after the start of emicizumab prophylaxis (visit 2). FVIII inhibitor titers were determined by the Bethesda assay, by using one-stage FVIII activity assay with Actin FS as aPTT reagent (before emicizumab prophylaxis) and chromogenic FVIII activity assay with bovine reagents (after introduction of emicizumab) (Siemens Healthcare Diagnostics, Marburg, Germany). Additionally, data about treatment with bypassing agents or FVIII concentrate were collected.

Results: The titer of FVIII inhibitors from ten adult PWHA (median age: 44 years; range: 27 – 65 years) during the follow-up period of median (range) of 36 (18-60) months is presented in Table 1. In seven out of ten patients inhibitor titers decreased after introduction of emicizumab, with medians (ranges) 2.7 (2.1-25.6 BU/mL) and 1.7 ( < 0.6-3.6 BU/mL), at the first and second visit, respectively, while in three patients the inhibitor titer remained negative. None of the patients had an increase of inhibitor titer. Four (40%) patients received at least one dose of rFVIIa, with no influence on inhibitor titer (Table 1), while none received either FVIII concentrate or aPCC.

Conclusion(s): Emicizumab prophylaxis resulted in spontaneous decrease or continuance of negativity of FVIII inhibitor titer in all PWHA and positive inhibitors or history of inhibitors.