Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors
Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors
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DOI：
10.1111/hae.12246
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发表时间：
2014-01-01
期刊：
影响因子：
3.9
通讯作者：
Wong, W. -Y.
中科院分区：
文献类型：
--
作者：
Antunes, S. V.;Tangada, S.;Wong, W. -Y.
用于治疗中度至重度A型和B型血友病的因子替代疗法可能因产生因子VIII（FVIII）或因子IX的抑制性同种抗体而复杂化。使用纳米过滤的抗抑制剂凝血复合物-因子八抑制剂释放活性（FEIBA NF）治疗是控制高滴度抑制剂或低滴度抑制剂替代治疗难治性患者急性出血的关键治疗选择。考虑到使用凝血因子VIII或修复体抑制剂的血友病患者的发病率和死亡率高风险，我们进行了这项3期前瞻性研究，以评估FEIBA NF预防是否是一种安全有效的治疗选择。在1年的时间内，17例受试者接受了主动治疗（85 +/-15 Ukg（-1），每隔一天），19例受试者接受了按需治疗。预防性治疗期间的中位（IQR）年出血率（ABR）为7.9（8.1），而按需治疗期间为28.7（32.3），降低了72.5%，两组间ABR存在统计学显著差异（P=0.0003）。3例（17.6%）接受预防性治疗的受试者（ITT）未发生出血事件，而按需治疗的受试者均未发生出血事件。按需治疗期间FEIBA NF治疗出血事件的总利用率显著高于预防性治疗（P=0.0067）。两组之间的相关不良事件发生率无差异。这项研究表明，与按需治疗相比，FEIBA预防性治疗显著减少了所有类型的出血，预防性治疗的安全性与按需治疗相当。
Factor replacement therapy for the treatment of moderate to severe haemophilia A and B can be complicated by the production of inhibitory alloantibodies to factor VIII (FVIII) or factor IX. Treatment with the nanofiltered anti-inhibitor coagulant complex, Factor Eight Inhibitor Bypassing Activity (FEIBA NF), is a key therapeutic option for controlling acute haemorrhages in patients with high-titre inhibitors or low-titre inhibitors refractory to replacement therapy. Given the high risk for morbidity and mortality in haemophilia patients with inhibitors to FVIII or FIX, we conducted this Phase 3 prospective study to evaluate whether prophylaxis with FEIBA NF is a safe and effective treatment option. Over a 1-year period, 17 subjects were treated prophylactically (85 +/- 15Ukg(-1) every other day) while 19 subjects were treated on demand. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 7.9 (8.1), compared to 28.7 (32.3) during on-demand treatment, which amounts to a 72.5% reduction and a statistically significant difference in ABRs between arms (P=0.0003). Three (17.6%) subjects (ITT) on prophylaxis experienced no bleeding episodes, whereas none treated on demand were bleeding episode-free. Total utilization of FEIBA NF for the treatment of bleeding episodes was significantly higher during on-demand therapy than prophylaxis (P=0.0067). There were no differences in the rates of related adverse events between arms. This study demonstrates that FEIBA prophylaxis significantly reduces all types of bleeding compared with on-demand treatment, and the safety of prophylaxis is comparable to that of on-demand treatment.