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

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.