Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice.

In this review article, we analyzed the definition, frequency, and severity of BTH events across phase 3 clinical trials with terminal (anti-C5 ravulizumab and crovalimab) and complement inhibitors upstream C5 (anti-C3 pegcetacoplan, alternative-pathway inhibitors iptacopan, and danicopan), as well as from real-world reports.

在这篇综述文章中，我们分析了在3期临床试验中，针对终端（抗C5 ravulizumab和crovalimab）和上游C5的补体抑制剂（抗C3 pegcetacoplan，替代途径抑制剂iptacopan和danicopan）以及来自真实世界报告的突破性溶血（BTH）事件的定义、频率和严重程度。

Furthermore, we reviewed the impact of the various compounds on quality of life and patient-reported outcomes.

此外，我们回顾了各种化合物对生活质量及患者报告结果的影响。

In particular, BTH may occur with all complement inhibitors, with a frequency of 10% to 15% over 6 months with eculizumab, crovalimab, and pegcetacoplan, and <5% with ravulizumab, iptacopan, and danicopan plus anti-C5.

特别是，BTH可能与所有补体抑制剂发生，使用依库珠单抗、克罗瓦利单抗和佩格塞塔单抗的患者在6个月内发生率为10%至15%，而使用拉库利珠单抗、伊普他单抗和达尼科单抗加抗C5的患者发生率则低于5%。

By prolonging the follow-up, the frequency of BTH appeared increased in patients treated with pegcetacoplan (nearly 24% at 1 year) as compared with both anti-C5, iptacopan, and double inhibition with danicopan plus anti-C5.

通过延长随访时间，接受Pegcetacoplan治疗的患者中BTH的发生频率似乎有所增加（1年时接近24%），与抗C5、iptacopan以及danicopan联合抗C5的双重抑制治疗相比。

BTH risk appears associated with patients' features, particularly suboptimal response/failure of previous complement inhibitor.

BTH风险似乎与患者的特征有关，特别是之前补体抑制剂的亚优反应/失败。

Transfusions were required in approximately half of cases and modifications of anticomplement therapy included anticipation of the next anti-C5 dose and addition of eculizumab in patients on proximal inhibitors.

大约一半的病例需要输血，抗补体治疗的调整包括提前下一次抗C5剂量和在使用近端抑制剂的患者中添加eculizumab。

Breakthrough thromboses were rare, although anticoagulant prophylaxis should be considered during severe episodes.

尽管在严重发作期间应考虑抗凝预防，但突破性血栓的发生率很低。

Complement amplifying conditions were observed in approximately half of cases and were more frequently infections.

大约一半的病例中观察到补体放大条件，且这些条件更常见于感染。

Treatment adherence, optimization of the administration schedule, anticoagulant prophylaxis, as well as education of patients and physicians remain important factors to prevent BTH and its complications.

治疗依从性、给药时间表的优化、抗凝预防以及患者和医生的教育仍然是预防BTH及其并发症的重要因素。