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Review
. 2025 May 11.
doi: 10.1007/s40620-025-02303-8. Online ahead of print.

Comparative efficacy of epoetin alfa vs. darbepoetin in children with chronic kidney disease: a systematic review, meta-analysis and cost-effectiveness analysis

Nicola Bertazza Partigiani  1   2 , Alessandro D'Uva  3   4 , Serena Vigezzi  3   4 , Alessandra Rosalba Brazzale  5 , Enrico Vidal  3   6
Affiliations
Review

Comparative efficacy of epoetin alfa vs. darbepoetin in children with chronic kidney disease: a systematic review, meta-analysis and cost-effectiveness analysis

Nicola Bertazza Partigiani et al. J Nephrol. .

Abstract

Background: Recombinant human erythropoietin (rHuEPO) and darbepoetin alfa (DA) are key treatments for anemia in individuals with chronic kidney disease (CKD), including children, but evidence comparing their efficacy in the pediatric population remains inconclusive.

Methods: This systematic review, adhering to PRISMA guidelines, analyzed randomized controlled trials and observational studies comparing rHuEPO and DA in pediatric patients with CKD (≤ 18 years; ≥ 10 children per study), searched across medical databases and clinical trial registries until 31/12/2024. The Cochrane Risk of Bias was used for assessment. Meta-analysis evaluated hemoglobin (Hb) increase and cost-effectiveness using the incremental cost-effectiveness ratio.

Results: From 1298 screened articles, 7 studies were included: 3 prospective studies, 2 randomized open-label non-inferiority trials, and 2 retrospective cohort studies, comprising 208 children for direct comparisons and 357 for transitioning studies. Meta-analysis found no significant Hb improvement differences between rHuEPO and DA after 21-28 weeks of treatment (DA + 0.15 g/dL, 95% CI - 0.22 to + 0.52). rHuEPO was more cost-effective than DA. Transitioning to DA increased Hb by + 0.93 g/dL (95% CI 0.53-1.33) in children with suboptimal levels, after 21-28 weeks of rHuEPO. The incremental cost-effectiveness ratio of switching to DA was ~ €340 per g/dL of Hb over 24 weeks.

Conclusions: rHuEPO is the most cost-effective initial anemia treatment in pediatric CKD. However, transitioning to DA may be considered for patients who do not achieve adequate Hb response. The small number of randomized controlled trials (RCTs), variability in dose conversion, and study heterogeneity may limit generalizability.

Prospero id: CRD42023460872.

Keywords: Anemia; Children; Chronic kidney disease; Erytropoiesis-stimulating agents.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no conflict of interest to declare. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Ethical approval: Ethical approval was not required since no new patients were recruited. The study was a meta-analysis based exclusively on already published data. Research involving human participants and/or animals: Not applicable. The present study is a literature-based meta-analysis. Informed consent to participate: This systematic review did not involve the collection of new data from participants, and therefore informed consent was not applicable. Data availability statement: The data underlying this manuscript are available in the article and in its online supplementary material. Funding: This work is being supported by the Research4Residents project within the Residency Program in Pediatrics at the University of Padova, Italy. Author contributions: Conceptualization: Bertazza Partigiani Nicola, Vidal Enrico; Methodology: D’Uva Alessandro, Vigezzi Serena, Bertazza Partigiani Nicola; Formal analysis and investigation: Bertazza Partigiani Nicola, Brazzale Alessandra Rosalba; Writing—original draft preparation: D’Uva Alessandro, Vigezzi Serena; Writing—review and editing: Bertazza Partigiani Nicola, Vidal Enrico; Supervision: Vidal Enrico.

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