Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) has infectious side effects in addition to its therapeutic benefits. The mechanism of development of infections, treatment modalities and preventive strategies for the associated infections have been discussed in this systematic review. The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and reporting guidelines. Inclusion and exclusion criteria were determined. A total of 18 research papers were extracted after exploring the databases from 2001 to 2024. The New Castle Ottawa Questionnaire for non-randomized clinical trials and observational studies, the National Institutes of Health (NIH) quality assessment tool for case reports and case series, and the scale for the quality assessment of narrative review articles checklist for literature review were used to assess the risk of bias. The bacteria causing infection secondary to eculizumab are Neisseria meningitidis, Neisseria gonorrhoeae, unusual Neisseria species, Moraxella lacunata, and Pseudomonas aeruginosa and fungus causing infection secondary to eculizumab is Aspergillus niger. Health care providers should maintain a high index of suspicion for these adverse effects for early identification and treatment.
Author(s) Details:
Ravneet K. Dhanoa
Department of Internal Medicine/Hematology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Ramaneshwar Selvaraj
Department of Internal Medicine/Family Medicine/General Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Shoukrie I. Shoukrie
Department of Orthopaedics/Traumatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Anam Zahra
Department of Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Jyothirmai Malla
Department of Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Tharun Yadhav Selvamani
Department of General Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Sathish Venugopal
Department of Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Ranim K. Hamouda
Department of Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Pousette Hamid
Department of Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Recent Global Research Developments in Infection Risks Associated with Eculizumab Therapy: A Systematic Review
Atypical Hemolytic-Uremic Syndrome (aHUS):
aHUS is a thrombotic microangiopathy characterized by mechanical hemolysis, renal impairment, thrombocytopenia, and preserved ADAMTS13 function.
It results from complement-mediated damage to the microvascular endothelium, affecting multiple organs.
Clinically significant disease requires a complement-amplifying trigger (e.g., infection, surgery, pregnancy, cancer, or autoimmunity).
Genetic variants in complement genes play a role in aHUS development.
Eculizumab and Treatment:
Eculizumab, a terminal complement inhibitor, has revolutionized aHUS management.
Previously, over 50% of patients died or developed end-stage renal disease within a year of diagnosis. C5 inhibitors (like eculizumab) reduce this figure to less than 15%.
Clinical improvement occurs within days to weeks after C5 inhibition, with most patients achieving complete or near-complete response after 3 to 6 months of therapy.
Discontinuation of Eculizumab:
A recent prospective phase 4 study found that discontinuing eculizumab is safe in most patients with aHUS once they achieve complete remission.
Risk of relapse was <25% overall, but higher (up to 50%) in patients with rare variants in complement genes.
An algorithm for discontinuing eculizumab may be considered based on individual patient factors [1] .
Other Risks Associated with Eculizumab:
Eculizumab is known to increase the risk of invasive meningococcal infection.
Rarely, it may result in disseminated gonococcal infection (DGI) [2] .
Additionally, it significantly increases the risk of infection with encapsulated bacteria and sepsis [4] .
References
- Eculizumab and aHUS: to stop or not
https://ashpublications.org/blood/article/137/18/2419/475859/Eculizumab-and-aHUS-to-stop-or-not - Saito, M., Harada, S., Ogasawara, R., Izumiyama, K., Mori, A., Morioka, M., & Kondo, T. (2020). Disseminated gonococcal infection associated with eculizumab therapy for paroxysmal nocturnal hemoglobinuria: a case report and literature review. International Journal of General Medicine, 403-406.
- Doubrovinskaja, S., Korporal-Kuhnke, M., Jarius, S. et al. Newly emerging type B insulin resistance (TBIR) during treatment with eculizumab for AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD): fatal outcome. J Neurol 271, 2866–2870 (2024). https://doi.org/10.1007/s00415-023-12071-9
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