Once-monthly darbepoetin alfa is non-inferior to biweekly dosing for maintaining target hemoglobin in erythropoiesis-stimulating agent-responsive Korean patients with non-dialysis chronic kidney disease: a multicenter phase 4 study

Background: Anemia is a common complication in patients with non-dialysis chronic kidney disease managed with erythropoiesis- stimulating agents. Although biweekly darbepoetin alfa administration is standard practice, extended-interval dosing may improve convenience and adherence and reduce hemoglobin overshoot risk. Methods: This prospective, single-arm, phase 4 study evaluated the non-inferiority, safety, and clinical feasibility of switching from biweekly to once-every-4-week darbepoetin alfa administration in patients with non-dialysis chronic kidney disease. Participants initially received biweekly dosing for 12 weeks (run-in), followed by once-every-4-week dosing for 12 weeks (evaluation). The primary outcome was the absolute change in hemoglobin during each period. Secondary outcomes included response frequency, rate within the target range (hemoglobin >10.0 to ≤11.0 g/dL), and incidence of hemoglobin >11.0 g/dL. Results: Forty patients completed the study. The absolute change in hemoglobin during once-every-4-week dosing (evaluation) was non-inferior to that observed during biweekly dosing (run-in) (mean difference, -0.140 g/dL; 95% confidence interval, -0.434 to 0.154; non-inferiority p = 0.03). The proportion of patients maintaining hemoglobin ≥10.0 g/dL at the end of the once-every-4-week dosing period was 75.0%, with the hemoglobin >11.0 g/dL incidence significantly decreasing from 35.0% to 15.0% (p = 0.02). Generalized estimating equations and post-hoc analyses confirmed significant temporal changes in overshooting patterns, with a stable within-target hemoglobin response. Conclusion: Once-every-4-week darbepoetin alfa administration is non-inferior to biweekly dosing for hemoglobin control in patients with non-dialysis chronic kidney disease and reduces the risk of hemoglobin overshooting. This supports the clinical utility of once-every- 4-week dosing following current anemia management guidelines.