用于治疗慢性肾脏病相关贫血的Vadadustat与Darbepoetin Alfa总体不良事件概况(第3阶段试验)
Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
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影响因子:3.2
分区:医学2区 / 泌尿学与肾脏学2区
发表日期:2022
作者:
Rajiv Agarwal, Sanjeev Anand, Kai-Uwe Eckardt, Wenli Luo, Patrick S Parfrey, Mark J Sarnak, Christine M Solinsky, Dennis L Vargo, Wolfgang C Winkelmayer, Glenn M Chertow
DOI:
10.1159/000528443
摘要
慢性肾脏病(CKD)患者常见贫血,其与生活质量差和心血管结局不良有关,治疗贫血也对医疗系统带来较大经济负担。虽然现有治疗方法效果良好,但使用促红细胞生成素类药物的标准治疗需要持续/反复注射,不易被非中心维护性血液透析患者接受或偏好。此外,研究中针对正常或接近正常血红蛋白水平的血红蛋白浓度,使用这些药物也引发了心血管事件和死亡风险增加的安全性担忧。口服活性的低氧诱导因子前酶羟化酶抑制剂Vadadustat,可能通过激活内源性促红细胞生成素的途径,提供优于促红细胞生成素的治疗优势。为全面评估Vadadustat在透析依赖和非依赖CKD相关贫血患者中的安全性,我们汇总了该阶段临床试验计划中四项试验(总计n = 7373)的人群安全数据,并比较了各治疗组的治疗相关不良事件(TEAEs)风险。在随机分配至Vadadustat或Darbepoetin Alfa的患者中,TEAEs发生率(88.9% vs. 89.3%)、严重不良事件(58.0% vs. 59.3%)以及导致死亡的TEAEs(16.1% vs. 16.2%)均类似,特定关注的不良事件(如心血管、肝脏及肿瘤相关事件)发生率亦无显著差异。在接受Vadadustat治疗的CKD相关贫血患者中,发生不良事件的比例与Darbepoetin Alfa组相似。
Abstract
Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of anemia in chronic kidney disease patients with erythropoiesis-stimulating agents requires chronic/ongoing injections, making the treatment less accessible or desirable to patients not treated by in-center maintenance hemodialysis. Furthermore, safety concerns, including an increased risk of cardiovascular events and mortality, have emerged from their use in studies targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production.To comprehensively analyze the safety profile of vadadustat in patients with dialysis-dependent and non-dialysis-dependent CKD-related anemia, we pooled the safety populations from each of the four trials in the phase 3 clinical program (n = 7,373) and compared the risk of treatment-emergent adverse events (TEAEs) for each treatment arm.In patients randomized to vadadustat versus darbepoetin alfa, rates of TEAEs (88.9% vs. 89.3%), treatment-emergent serious adverse events (58.0% vs. 59.3%), and TEAEs leading to death (16.1% vs. 16.2%) were similar, as were rates of adverse events of special interest, including cardiovascular-, hepatic-, and neoplasm-related adverse events.Among patients with CKD-related anemia treated with vadadustat, we observed similar rates of adverse events relative to those treated with darbepoetin alfa.