Kessakorn Nuchanun, Gosriwatana Itsaraet, Sasipong Nuttarak, Srichumpuang Chonlatis, Moonla Chatphatai, Sosothikul Darintr
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Integrative and Innovative Hematology/Oncology Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Haemophilia. 2025 Jan;31(1):122-131. doi: 10.1111/hae.15146. Epub 2024 Dec 31.
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.
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.
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.
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.
ClinicalTrials.gov identifier NCT06155955.
皮下注射的emicizumab是一种模拟凝血因子VIII（FVIII）的双特异性单克隆抗体，可有效预防有/无抑制剂的甲型血友病（HA）患者出血；然而，其标准剂量方案费用高昂。在资源有限的环境中，低剂量emicizumab预防方案可用于无抑制剂的HA患者。
2023年期间，纳入了接受低/中剂量FVIII二级预防≥8个月的泰国无抑制剂重度HA或有严重出血表型的中度HA患者（常规FVIII预防前的历史年化出血率[ABR]>5次出血/年）。在4天的洗脱期后，实施低剂量emicizumab预防方案（每两周2.0-2.5mg/kg，共两次负荷剂量，然后每4周一次），持续8个月。分析emicizumab预防前后的ABR、年化关节出血率（AJBR）、血友病关节健康评分（HJHS）和血友病特异性生活质量（QoL）评分。还监测了改良一期FVIII检测中的emicizumab血浆水平。
15名受试者中，转换为低剂量emicizumab预防后，ABR（差异中位数，-2次出血/年；四分位间距，-3至0；p = 0.002）降低，但AJBR未降低（p = 0.07），尽管自第12周起达到的稳态前剂量emicizumab血浆水平适中（每月中位数水平，8.4µg/mL；四分位间距，4.3-10.4）。同时，HJHS（p = 0.008）和QoL评分（p < 0.001）降低，46.7%的患者在接受低剂量emicizumab时无出血。
与低/中剂量FVIII二级预防相比，低剂量emicizumab可显著改善无抑制剂重度HA或有严重出血表型的中度HA患者的出血预防、关节健康和生活质量。该方案可能有助于满足中低收入国家HA护理中以前未满足的需求。
ClinicalTrials.gov标识符NCT06155955。
