A systematic review and meta-analysis suggests an individualized treatment plan for eculizumab-refractory paroxysmal nocturnal hemoglobinuria (PNH) based on eculizumab refractoriness and the mechanism of PNH breakthrough.

The review and meta-analysis, published in SAGE Open Medicine, found few well-powered studies and limited evidence to guide the management of eculizumab-refractory PNH.

“Eculizumab, an anti-complement monoclonal antibody was approved by the FDA in 2007 for the treatment of PNH and has been the backbone for its treatment for many years,“ the authors wrote. “The aim of this study was to conduct a systematic review on the available literature on the treatment modalities available for the management of eculizumab refractory PNH.”

The research team conducted a systematic review and meta-analysis of studies in the PubMed and Scopa databases, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on April 19, 2022. Of 70 articles on eculizumab-refractory PNH in total, 4 met the search criteria and were analyzed.

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Two of the analyzed studies were from 2021 and 2 were from 2020, showing the novelty of the drugs assessed (danicopan, iptacopan, and pegcetacoplan) and their use in eculizumab refractory PNH. All studies reported on multicenter clinical trials, phases I, II, and III.

The studies suggested that the drugs assessed improved control of hemolysis and had fewer side effects compared with eculizumab. Pegcetacoplan resulted in increased protection from complement-activated hemolysis, and danicopan and iptacopan were preferred by patients due to their oral administration route.

The authors caution that there are as yet no clear guidelines for treatment of eculizumab-refractory PNH. Furthermore, only 2 databases were searched, and the small patient sample sizes limit the generalizability of the results. However, they recommend a tailored treatment plan based on the mechanism of PNH breakthrough and the mechanism of eculizumab refractoriness for these patients.


Syed S, Khan R, Khurram F, Khan FH, Safi D, Ud Din Safi S. Treatment of eculizumab refractory paroxysmal nocturnal hemoglobinuria: a systematic review about current treatment options and future direction. SAGE Open Med. Published online June 22, 2023. doi:10.1177/20503121231181267