Vadadustat与Darbepoetin alfa的总体不良事件特征，用于治疗与慢性肾脏疾病相关的贫血，在第三阶段试验中
Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
影响因子:3.20000
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
摘要
贫血经常发生在慢性肾脏疾病（CKD）中，与生活质量和心血管结局差有关，其治疗代表了医疗保健系统的巨大经济负担。尽管有效，但目前在慢性肾脏疾病患者患有红细胞生成剂的慢性肾病患者中治疗贫血的护理标准需要慢性/持续的注射，这使得治疗对未经中心维持血液疗法治疗的患者易于访问或理想。此外，安全问题，包括增加心血管事件和死亡率的风险增加，它们来自于针对正常或近正常范围内血红蛋白浓度的研究中的使用。口头活跃的低氧诱导因子脯氨酰羟化酶抑制剂Vadadustat可能通过通过途径通过途径纠正贫血来纠正贫血，从而提供比促红细胞生成的优势，从而可以全面地激活内源性促红细胞生成素的产生。第三阶段临床计划中四个试验中每个试验中的每个试验的安全群体（n = 7,373），并比较了每个治疗部门的治疗征服不良事件（TEAE）的风险。 （16.1％比16.2％）是相似的，以及包括心血管，肝，肝和肿瘤相关的不良事件在内的不良事件的发生率也相似。与vadadustat治疗的CKD相关贫血患者，我们观察到了与Darbepoetinalfa的患者相似的不良事件。
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.