The MAPTO survey: worldwide approaches on unmasking factor VIII inhibitors in children with emicizumab treatment: communication from the ISTH SSC Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders

Abstract

It might take years for previously untreated patients (PUPs) with hemophilia A on emicizumab prophylaxis to receive 50 factor VIII (FVIII) exposures. This corresponds to the time at risk for FVIII inhibitors under conventional FVIII prophylaxis. During emicizumab prophylaxis, it is unknown whether additional treatment with regular FVIII doses promotes FVIII tolerance, unmasks inhibitors, or rather, induces them. Therefore, we conducted a survey to describe the current global perspectives and practices of hemophilia health care providers (HCPs) in PUPs with severe hemophilia A receiving emicizumab prophylaxis. In 2024, a survey was sent by email to 1193 hemophilia treatment centers, addressing the perceived inhibitor risk with emicizumab, the potential need for concomitant regular FVIII infusions, and the perceived parental willingness to use concomitant FVIII. In total, 102 pediatric HCPs (85% physicians, 13% nurses) from 38 countries participated. Perceived inhibitor risk data were available for 63 HCPs (62%). Compared with FVIII prophylaxis, the inhibitor risk on emicizumab was estimated to be higher by 13%, equal by 41%, lower by 32%, and unknown by 14%. Among 57 of 102 HCPs with clinical access to emicizumab for children with severe hemophilia A without inhibitors, 30 (53%) offered regular concomitant FVIII infusions. However, in the experience of the HCPs, approximately 45% of parents rejected this option due to concerns about intravenous access. Ultimately, global perspectives on FVIII inhibitor risk and concomitant FVIII use in PUPs on emicizumab prophylaxis are heterogeneous due to lack of evidence, indicating the need for further research to guide treatment strategies.