Switching to Pegmolesatide in Maintenance Dialysis: Real-World Hemoglobin Response, Temporal Dynamics, and Modality-Specific Predictors.

IF 6.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2026-10-01 eCollection Date: 2026-01-01 DOI:10.2147/DDDT.S632477

Chunlei Luo, Sizeng Bao, Yuanyuan Ai, Lingling Bao, Ruijuan Wang, Jianwei Ma, Xueyan Bian

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引用次数: 0

Abstract

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.

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维护性透析改用聚乙二醇塞肽：真实世界血红蛋白反应、时间动态和模式特异性预测因子。

目的：Pegmolesatide是用于肾性贫血的每月皮下促红细胞生成素模拟肽，但除了随机试验之外的实际数据仍然很少。我们评估了其有效性、时间反应动态和模式特异性反应预测因子，用于从既往贫血治疗切换到维持透析的患者。患者和方法：在这项单中心回顾性研究中，分析了192例维持性透析患者（血液透析[HD]， n = 90；腹膜透析[PD]， n = 102），每月接受皮下培莫塞肽；52.6%的患者不再使用促红细胞生成素，47.4%的患者不再使用缺氧诱导因子丙氨酸羟化酶抑制剂，主要是为了控制贫血。主要终点是第3个月时血红蛋白（Hb）的变化。次要终点包括铁动力学、时间模式的混合效应建模（1423个观察值）和不良反应预测因子。结果：在第3个月时，平均Hb从96.4±15.9 g/L增加到110.0±19.2 g/L(模型估计Δ = +13.0 g/L; 95% CI， 9.8至16.3；结论：每月服用聚莫塞肽与Hb的快速持续改善和可接受的安全性相关。基线Hb和透析时间是主要的反应预测因子，具有不同的模式特异性概况，支持随机试验中个体化给药策略的评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.