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

IF 3 2区医学 Q2 HEMATOLOGY Haemophilia Pub Date : 2024-12-31 DOI:10.1111/hae.15146

Nuchanun Kessakorn, Itsaraet Gosriwatana, Nuttarak Sasipong, Chonlatis Srichumpuang, Chatphatai Moonla, Darintr Sosothikul

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Abstract

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.

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低剂量Emicizumab与低/中剂量因子VIII二级预防治疗严重出血表型的非抑制剂血友病A患者

背景：皮下emicizumab是一种模拟因子VIII （FVIII）的双特异性单克隆抗体，可有效预防有/无抑制剂的血友病a （HA）患者出血；然而，其标准剂量方案在财政上负担沉重。在资源有限的情况下，低剂量emicizumab预防可以替代地应用于非抑制剂HA患者。方法：在2023年期间，纳入接受低/中剂量FVIII二级预防≥8个月的泰国非抑制剂严重HA或中度HA伴严重出血表型（常规FVIII预防前的历史年化出血率[ABR] bb50例/年出血）的患者。在4天的洗脱期后，低剂量emicizumab预防（每两周2.0-2.5 mg/kg，两次负荷剂量，然后每4周）实施8个月。分析了半蜜单抗前/后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。改良一期FVIII试验的Emicizumab血浆水平也被监测。结果：15例患者ABR(差异中位数，2次出血/年；四分位数范围，-3到0；p = 0.002)，但改用低剂量emicizumab预防后，AJBR没有减少（p = 0.07），尽管自第12周以来，剂量前emicizumab在稳定状态下的血浆水平是适度的(月中位水平，8.4 μ g/mL；四分位数范围4.3-10.4)。结论：与低/中剂量FVIII二级预防相比，低剂量emicizumab可显著改善伴有严重出血表型的非抑制剂重度HA或中度HA患者的出血预防、关节健康和生活质量。这一方案可能有助于解决中低收入国家以前未满足的医管局护理需求。试验注册：ClinicalTrials.gov标识符NCT06155955。

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来源期刊

Haemophilia 医学-血液学

CiteScore

6.50

自引率

28.20%

发文量

226

审稿时长

3-6 weeks

期刊介绍： Haemophilia is an international journal dedicated to the exchange of information regarding the comprehensive care of haemophilia. The Journal contains review articles, original scientific papers and case reports related to haemophilia care, with frequent supplements. Subjects covered include: clotting factor deficiencies, both inherited and acquired: haemophilia A, B, von Willebrand''s disease, deficiencies of factor V, VII, X and XI replacement therapy for clotting factor deficiencies component therapy in the developing world transfusion transmitted disease haemophilia care and paediatrics, orthopaedics, gynaecology and obstetrics nursing laboratory diagnosis carrier detection psycho-social concerns economic issues audit inherited platelet disorders.