OC 71.3 - Low-dose emicizumab versus low-dose factor VIII secondary prophylaxis for noninhibitor hemophilia A patients with severe bleeding phenotype

Background: Due to activated factor VIII (FVIII)-mimicking functions, subcutaneous administration of emicizumab every 1-4 weeks effectively prevents bleeds in patients with hemophilia A (HA) with/without inhibitors. However, its standard regimens can cause a financial burden, especially for resource-constrained settings

Aims: To study the clinical impact and pharmacokinetic profile of low-dose emicizumab prophylaxis after switching from low-dose FVIII prophylaxis in Thai noninhibitor HA patients.

Methods: During 2022-2023, noninhibitor patients with severe HA or moderate HA with severe bleeding phenotype (annualized bleeding rate (ABR) >5 bleeds/year during on-demand treatment) who received low-dose FVIII prophylaxis ≥8 months were enrolled. After the 4-day washout period, low-dose emicizumab prophylaxis (2.0-2.5 mg/kg every 2 weeks for 2 doses followed by every 4 weeks) was implemented for 8 months. Between the 2 prophylactic periods, ABR, annualized joint bleeding rates (AJBR), hemophilia joint health scores (HJHS), and hemophilia-specific quality-of-life (QoL) scores by Haemo-QoL or Haemo-QoL-A questionnaires were compared. Using standard one-stage FVIII assay, pre-dose emicizumab plasma level approximation (ELA) was monitored throughout the study.

Results: In 15 eligible subjects (mean age 14.3±7.8 years; 33.3% with target joints), ABR, HJHS, and QoL scores, but not AJBR, were significantly reduced after switching to low-dose emicizumab prophylaxis (Table 1). The steady state of ELA was achieved after 3 emicizumab administrations, with a median monthly ELA of 7.2% (interquartile range, 5.1-10.1) at 12 weeks (Figure 1). Activated partial thromboplastin times at 12 weeks were also normalized (median, 28.2; interquartile range, 25.3-28.8), correlated with hemostatic properties on rotational thromboelastometry. Overall, 46.7% of the patients, including 2 patients with very low ELA ( < 2.0%), had zero bleeds during low-dose emicizumab prophylaxis.

Conclusion(s): Low-dose emicizumab compared to low-dose FVIII prophylaxis improves bleeding prevention, joint health, and QoL in noninhibitor HA patients with severe bleeding phenotype. This regimen may potentially help address previously unmet needs in HA care among low-to-middle-income countries.