Abstract / Summary
Purpose: Pegmolesatide is a monthly subcutaneous erythropoietin mimetic peptide for renal anemia, but real-world data beyond randomized trials remain scarce. We evaluated its effectiveness, temporal response dynamics, and modality-specific response predictors in maintenance dialysis patients switched from prior anemia therapy. Patients and Methods: In this single-center retrospective study, 192 maintenance dialysis patients (hemodialysis [HD], n = 90; peritoneal dialysis [PD], n = 102) receiving monthly subcutaneous pegmolesatide were analyzed; 52.6% had switched from erythropoiesis-stimulating agents and 47.4% from a hypoxia-inducible factor prolyl hydroxylase inhibitor, predominantly for suboptimal anemia control. The primary endpoint was hemoglobin (Hb) change at month 3. Secondary endpoints included iron dynamics, mixed-effects modeling of temporal patterns (1,423 observations), and predictors of poor response. Results: Mean Hb increased from 96.4 ± 15.9 to 110.0 ± 19.2 g/L at month 3 (model-estimated Δ = +13.0 g/L; 95% CI, 9.8 to 16.3; P< 0.001) and remained stable through month 12. Target achievement (Hb ≥ 110 g/L) rose from 19.8% to 54.5%. The Hb trajectory was nonlinear, with a rapid first-month rise followed by deceleration; increments were attenuated at higher baseline Hb (ceiling effect), and higher serum albumin was associated with faster Hb improvement. Iron deficiency declined from 46.3% at baseline to a model-estimated 20.4% at month 12. Higher baseline Hb predicted a smaller increment; dialysis vintage of 12– 36 months independently predicted attenuated response (pooled OR 5.17– 8.68; P< 0.001). Predictors differed by modality (body mass index in HD; diabetes in PD). Thromboembolic events (2.6%) were exclusively vascular access-related; mortality was 2.1%. Conclusion: Monthly pegmolesatide was associated with rapid and sustained Hb improvement and acceptable safety. Baseline Hb and dialysis vintage were the dominant response predictors, with distinct modality-specific profiles, supporting evaluation of individualized dosing strategies in randomized trials. Keywords: pegmolesatide, dialysis, anemia, iron metabolism, response dynamics