Post‑Marketing Surveillance of the Safety and Effectiveness of Emicizumab in Japanese Patients With Congenital Haemophilia A With Inhibitors.

INTRODUCTION

The bispecific monoclonal antibody emicizumab was approved for prophylactic treatment of congenital haemophilia A (HA) in Japan in 2018.

AIM: To monitor long-term safety and effectiveness of emicizumab, including appropriate concomitant use of bypassing agents (BPAs), in Japanese patients with congenital HA with inhibitors who initiated emicizumab within 1 year of availability.

METHODS

This all-case post-marketing surveillance (PMS) study was conducted between May 2018 and January 2023, in patients of all ages and HA severities. Patients were registered retrospectively after emicizumab initiation or prospectively at the time of initiation. Adverse events (AEs) and adverse drug reactions (ADRs), including thromboembolic events (TEs) and thrombotic microangiopathy (TMA), and their association with BPA use, were examined. FVIII inhibitor levels and annualised bleeding rates (ABRs) were evaluated.

RESULTS

In total, 134 patients were included in the analysis. Mean (standard deviation) duration of emicizumab treatment was 145.5 (34.8) weeks. Overall, 112 AEs occurred in 47 patients (35.1%) and 22 ADRs occurred in 12 patients (9.0%); 8 ADRs (36.4%) were serious. No TEs/TMAs associated with concomitant use of BPAs occurred. FVIII inhibitor levels remained stable or decreased for 34 patients (55.7%). Sixty-eight patients (50.7%) received BPAs; none received activated prothrombin complex concentrate. Mean (95% confidence interval) model-based all bleed ABR and treated bleed ABR were 1.4 (0.9-2.3) and 1.3 (0.8-2.1), respectively.

CONCLUSION

This study comprises 3 years' PMS for emicizumab. No TEs/TMA associated with BPAs occurred. Results further support the safety and effectiveness of emicizumab in Japanese patients with congenital HA with inhibitors.