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Review
. 2025 May 8;184(6):331.
doi: 10.1007/s00431-025-06160-2.

Eculizumab in severe pediatric STEC-HUS and its impact on neurological prognosis-a systematic review and meta-analysis

Rachele Spagnol  1 , Alessandra Alfisi  2 , Marco Moi  2 , Ilaria Bonvecchio  2 , Nicola Bertazza Partigiani  2 , Enrico Vidal  2   3
Affiliations
Review

Eculizumab in severe pediatric STEC-HUS and its impact on neurological prognosis-a systematic review and meta-analysis

Rachele Spagnol et al. Eur J Pediatr. .

Abstract

Hemolytic-uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is caused, in 90% of pediatric cases, by Shiga toxin-producing Escherichia coli (STEC-HUS) infection. While targeting complement component C5 using eculizumab has shown benefit in atypical HUS, its effect on STEC-HUS, especially on neurological outcome, remains unclear. This systematic review and meta-analysis aimed to evaluate the impact of eculizumab on neurological prognosis in pediatric STEC-HUS. The review was conducted in accordance with PRISMA guidelines and was registered in PROSPERO (CRD42024496489). A comprehensive literature search was performed in Embase, MEDLINE, Cochrane Library, CINAHL, clinicaltrial.gov, and grey literature sources up to February 28, 2025. Original studies involving pediatric patients (0-18 years) with STEC-HUS and neurological complications, treated with eculizumab, were eligible. Two independent reviewers screened studies and extracted data. Seven studies were included, totaling 529 patients, of whom 135 (25.5%) developed neurological complications. Among these, 44 patients (32.5%) had received eculizumab. Meta-analysis showed a higher likelihood of receiving eculizumab therapy in patients with neurological involvement compared to those without (OR 13.03, 95% CI 4.40-38.75). However, in patients with neurological involvement, no clinical benefit was observed compared to those treated with standard therapies (OR 0.32, 95% CI 0.09-1.22, p = 0.10).

Conclusion: Our data did not demonstrate a significant improvement in neurological outcomes for STEC-HUS patients treated with eculizumab. Findings are limited by retrospective designs and potential confounding by indication; therefore, further studies are needed.

What is known: • Neurological involvement is a major contributor to morbidity in HUS, particularly in STEC-associated forms. • Eculizumab is sometimes used off-label in severe cases, although its effectiveness in this setting remains uncertain.

What is new: • This is the first systematic review and meta-analysis specifically addressing neurological prognosis in STEC-HUS. • Current evidence does not demonstrate a clear neurological benefit of eculizumab over standard therapy, highlighting the need for further studies.

Keywords: Eculizumab; Neurological involvement; Neurological outcome; STEC-HUS.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA 2020 flowchart for selection of studies
Fig. 2
Fig. 2
Risk of receiving eculizumab according to the presence of neurological involvement. NI +, patients with neurological involvement; ECU +, patients receiving eculizumab; ECU −, patients not receiving eculizumab
Fig. 3
Fig. 3
Likelihood of achieving an improved neurological outcome following eculizumab treatment. NI +, patients with neurological involvement; ECU +, patients receiving eculizumab; ECU −, patients not receiving eculizumab. N.Imp., neurological improvement
Fig. 4
Fig. 4
Funnel plot evaluating publication bias for the outcome “association between neurological involvement and eculizumab administration” (a) and “neurological involvement following eculizumab administration” (b)
Fig. 5
Fig. 5
Summary of findings with GRADE criteria
See this image and copyright information in PMC

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