Treatment of eculizumab refractory paroxysmal nocturnal hemoglobinuria: A systematic review about current treatment options and future direction

SAGE Open Med. 2023 Jun 22:11:20503121231181267. doi: 10.1177/20503121231181267. eCollection 2023.


Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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 of evidence: Level I.

Keywords: Paroxysmal nocturnal hemoglobinuria; eculizumab; refractory; review.

Publication types

  • Review