Low‐Dose Emicizumab Versus Low‐/Intermediate‐Dose Factor VIII Secondary Prophylaxis for Noninhibitor Haemophilia A Patients With Severe Bleeding Phenotype

BACKGROUND: Subcutaneous emicizumab, a factor VIII (FVIII)-mimicking bispecific monoclonal antibody, can effectively prevent bleeds in haemophilia A (HA) patients with/without inhibitors; however, its standard-dose regimens are financially burdensome. Low-dose emicizumab prophylaxis may alternatively be applied to noninhibitor HA patients in resource-limited settings. METHODS: During 2023, Thai patients with noninhibitor severe HA or moderate HA with severe bleeding phenotype (historical annualized bleeding rate [ABR] >5 bleeds/year before regular FVIII prophylaxis) who received low-/intermediate-dose FVIII secondary prophylaxis ≥8 months were enrolled. After the 4-day washout period, low-dose emicizumab prophylaxis (2.0-2.5 mg/kg every fortnight for two loading doses, then every 4 weeks) was implemented for 8 months. Pre-/post-emicizumab ABR, annualized joint bleeding rates (AJBR), haemophilia joint health scores (HJHS) and haemophilia-specific quality-of-life (QoL) scores were analysed. Emicizumab plasma levels on modified one-stage FVIII assays were also monitored. RESULTS: In 15 subjects, ABR (median of differences, -2 bleeds/year; interquartile range, -3 to 0; p = 0.002), but not AJBR (p = 0.07), were reduced after switching to low-dose emicizumab prophylaxis, although the pre-dose emicizumab plasma levels at the steady state, achieved since week 12, were modest (median monthly level, 8.4 µg/mL; interquartile range, 4.3-10.4). Concurrently, HJHS (p = 0.008) and QoL score (p < 0.001) were decreased, and 46.7% had zero bleeds while receiving low-dose emicizumab. CONCLUSIONS: Low-dose emicizumab, compared to low-/intermediate-dose FVIII secondary prophylaxis, meaningfully improves bleeding prevention, joint health and QoL in patients with noninhibitor severe HA or moderate HA with severe bleeding phenotype. This regimen potentially helps address previously unmet needs in HA care among low-to-middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06155955.