Syed Saad, Khan Reda, Khurram Fahmida, Khan Faiza Humayun, Safi Danish, Safi Salah Ud Din
College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE.
Crescent Cardiology Associates, Frisco, TX, USA.
SAGE Open Med. 2023 Jun 22;11:20503121231181267. doi: 10.1177/20503121231181267. eCollection 2023.
C5 inhibitors such as eculizumab and ravulizumab are the first-line treatment in the management of paroxysmal nocturnal hemoglobinuria (PNH). However, some patients develop novel symptoms as part of their treatment with eculizumab, and the disease is termed as eculizumab refractory PNH. The aim of this study was to conduct a systematic review on the available treatment modalities for the management of eculizumab refractory PNH.
Two authors independently searched two databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 70 studies were obtained: 4 out 70 studies were found to meet the inclusion criteria.
Four studies were found to meet the inclusion criteria of our study. Two studies were published in 2021 and two studies were published in 2020. All four studies were multicenter clinical trials. Two studies were phase III clinical trials, one study was a phase II clinical trial, and one study was a phase I clinical trial. Two studies were about pegcetacoplan, one was about danicopan, and one was about iptacopan.
Based upon the findings of our systematic review, we recommend an individualized treatment plan based on the mechanism of eculizumab refractoriness and the mechanism of PNH breakthrough. This recommendation is subject to the available resources and clinical expertise available at different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs should be performed to accurately assess the different medications and aid in designing guidelines of the management of eculizumab refractory PNH.
Level I.
依库珠单抗和ravulizumab等C5抑制剂是阵发性夜间血红蛋白尿（PNH）治疗的一线用药。然而，部分患者在接受依库珠单抗治疗时出现了新症状，这种疾病被称为依库珠单抗难治性PNH。本研究的目的是对依库珠单抗难治性PNH的现有治疗方式进行系统评价。
两名作者根据系统评价和Meta分析的首选报告项目指南，独立检索了两个数据库。共获得70项研究：70项研究中有4项符合纳入标准。
发现4项研究符合我们的纳入标准。2项研究于2021年发表，2项研究于2020年发表。所有4项研究均为多中心临床试验。2项研究为III期临床试验，1项研究为II期临床试验，1项研究为I期临床试验。2项研究关于pegcetacoplan，1项研究关于danicopan，1项研究关于iptacopan。
基于我们系统评价的结果，我们建议根据依库珠单抗难治性机制和PNH突破机制制定个体化治疗方案。该建议取决于不同医院的可用资源和临床专业知识。应开展更多采用随机对照试验等研究设计比较多种药物的研究，以准确评估不同药物，并有助于制定依库珠单抗难治性PNH的管理指南。
I级。
