Safety of recombinant activated factor VII for treatment of breakthrough bleeds in patients with congenital haemophilia A and inhibitors receiving emicizumab prophylaxis: Review of the real-world evidence

Abstract

Background: Emicizumab is used as a subcutaneous prophylaxis for prevention of bleeding episodes in patients with haemophilia A (HA) with and without inhibitors. While low bleeding rates were observed in clinical trials, patients still experience breakthrough bleeds (BTBs) with emicizumab in the real-world. Current guidelines recommend use of recombinant activated factor VII (rFVIIa) for treatment of BTBs in patients with inhibitors. Due to thrombotic events observed in the HAVEN 1 study, activated prothrombin complex concentrate (aPCC) should be used with caution. Objectives: The objective of this review is to identify and discuss real-world data on the frequency of BTBs and the safety of concomitant rFVIIa use in patients with inhibitors on emicizumab prophylaxis. Methods: A search of the following databases was conducted on 15 July 2022: BIOSIS Previews®, Current Contents Search®, Embase®, MEDLINE®. Search terms included ‘real world’, ‘haemophilia A’, and ‘emicizumab’. Results and conclusions: Eleven relevant publications were identified (seven original research articles and four congress abstracts). The frequency of BTBs specifically for HA patients with inhibitors was described in three publications with 5%–56% patients on emicizumab reporting ≥1 bleeding episode. Treatment of these BTBs appeared to be managed according to relevant guidelines. Importantly, no thrombotic complications occurred during concomitant rFVIIa use. Due to the nature of real-world studies, direct comparison of the results between studies is limited. However, real-world data show that BTBs in inhibitor patients during emicizumab prophylaxis can be safely treated with rFVIIa.