Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 14:14:20406207231216080.
doi: 10.1177/20406207231216080. eCollection 2023.

Efficacy of complement inhibitors for patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis

Jiyeon Lee  1   2 , Haeseon Lee  1   2 , Siin Kim  3 , Hae Sun Suh  1   2   4
Affiliations
Review

Efficacy of complement inhibitors for patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis

Jiyeon Lee et al. Ther Adv Hematol. .

Abstract

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan has revolutionized the management of PNH, leading to improvements in overall survival and quality of life for patients.

Objectives: This systematic review aims to provide comprehensive evidence of the efficacy of complement inhibitors in relation to treatment duration.

Design: This is a systematic review and meta-analysis.

Data sources and methods: A thorough literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library up to 3 May 2022. We included all prospective interventional studies including single-arm trials. The primary outcomes of interest were lactate dehydrogenase (LDH) levels, hemoglobin (Hb) concentrations, transfusion avoidance, and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores.

Results: Our study included a total of 27 studies, comprising 5 randomized controlled trials and 11 single-arm trials, with a total of 912 patients with PNH. We stratified the studies according to treatment duration, based on the most frequently reported period of 26 weeks. Our analysis showed that treatment-naïve patients who received complement inhibitors had a pooled estimate of a decrease in LDH levels from baseline by -1462.0 U/L (95% CI: -1735.6 to -1188.5) for treatment ⩽26 weeks and -1696.5 U/L (95% CI: -2122.7 to -1270.2) for treatment >26 weeks. The mean Hb levels were increased by 1.4 g/dL (95% CI: 0.5-2.3) and 1.9 g/dL (95% CI: 0.7-3.1) in each group. Treatment with any complement inhibitor prevented the need for transfusion in at least 50% of patients with PNH in all treatment periods. Clinically meaningful improvements in FACIT-F were observed both before and after 26 weeks, with a pooled estimate of 6.8 (95% CI: 6.0-7.6) and 9.5 (95% CI: 7.0-12.0), respectively.

Conclusion: Our findings suggest that complement inhibitors can result in positive treatment outcomes and sustained benefits for patients with PNH.

Keywords: clinical outcomes; complement inhibitors; eculizumab; paroxysmal nocturnal hemoglobinuria; pegcetacoplan; rare disease; ravulizumab.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Study flow chart based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline.
Figure 2.
Figure 2.
Forest plot of LDH outcomes. (a) Pooled effect of complement inhibitors on LDH concentration in treatment-naïve PNH patients (⩽26 weeks) and (b) pooled effect of complement inhibitors on LDH concentration in treatment-naïve PNH patients (>26 weeks). LDH, lactate dehydrogenase; PNH, paroxysmal nocturnal hemoglobinuria.
Figure 3.
Figure 3.
Forest plot of hemoglobin outcomes. (a) Pooled effect of complement inhibitors on Hb concentration in treatment-naïve PNH patients (⩽26 weeks) and (b) pooled effect of complement inhibitors on Hb concentration in treatment-naïve PNH patients (>26 weeks). Hb, hemoglobin; PNH, paroxysmal nocturnal hemoglobinuria.
Figure 4.
Figure 4.
Forest plot of transfusion outcomes. (a) Pooled effect of complement inhibitors on transfusion avoidance in treatment-naïve PNH patients (⩽26 weeks) and (b) pooled effect of complement inhibitors on transfusion avoidance in treatment-naïve PNH patients (>26 weeks). PNH, paroxysmal nocturnal hemoglobinuria.
Figure 5.
Figure 5.
Forest plot of FACIT-F outcomes. (a) Pooled effect of complement inhibitors on FACIT-F score in treatment-naïve PNH patients (⩽26 weeks) and (b) pooled effect of complement inhibitors on FACIT-F score in treatment-naïve PNH patients (>26 weeks). FACIT-F, Functional Assessment of Chronic Illness Therapy Fatigue; PNH, paroxysmal nocturnal hemoglobinuria.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Hill A, DeZern AE, Kinoshita T, et al.. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers 2017; 3: 17028. - PMC - PubMed
    1. Sahin F, Ozkan MC, Mete NG, et al.. Multidisciplinary clinical management of paroxysmal nocturnal hemoglobinuria. Am J Blood Res 2015; 5: 1–9. - PMC - PubMed
    1. Brodsky RA, Hu R. PIG-A mutations in paroxysmal nocturnal hemoglobinuria and in normal hematopoiesis. Leuk Lymphoma 2006; 47: 1215–1221. - PubMed
    1. Martí-Carvajal AJ, Anand V, Cardona AF, et al.. Eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria. Cochrane Database Syst Rev 2014; 10: CD010340. - PubMed
    1. Santarone S, Bacigalupo A, Risitano AM, et al.. Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Haematologica 2010; 95: 983. - PMC - PubMed

LinkOut - more resources