A real-world pharmacovigilance analysis of the FDA adverse event reporting system database for emicizumab

Abstract

Background and objectives

Emicizumab has fundamentally changed the clinical management of hemophilia A. Despite its benefits, concerns about adverse events (AEs) have risen. This retrospective study used disproportionality analysis of FAERS data from 2017 to 2023 to examine AEs associated with emicizumab, either alone or in combination with activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa), as well as the timing of these AEs.

Methods

Established algorithms (ROR, PRR, BCPNN, and MGPS) were used to assess correlations and calibrated p-values.

Results

Based on 1198 AEs, we identified 126 cases that met four algorithmic criteria. AEs associated with emicizumab included primarily joint pain and injection site reactions (ISRs), consistent with the drug label. Additionally, we observed thrombotic events related to emicizumab's black box warning. Specifically, we found that emicizumab poses increased risks of thrombosis when used in conjunction with aPCC or rFVIIa to treat breakthrough bleeds. After excluding reports related to the progression of hemophilia, we obtained 850 AEs with reported onset times. The median onset time for AEs was 106 days, with 46.59 % occurring within the first 90 days of emicizumab treatment.

Conclusion

Our study demonstrates the importance of early monitoring and interventions to minimize AEs and alleviate patient suffering.