{"title":"范式转变:随机对照试验元分析中探索依那曲达治疗慢性肾病贫血的方法","authors":"Lokman Hekim Tanrıverdi , Ahmet Sarıcı","doi":"10.1016/j.htct.2024.04.012","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Anemia commonly accompanies chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs), such as darbepoetin, are initiated for anemia in CKD. Additionally, hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors have demonstrated efficacy in treating CKD-associated anemia. This meta-analysis aims to compare the efficacy, safety, and tolerability of enarodustat in anemic CKD patients.</p><p><strong>Case report</strong></p></div><div><h3>Methodology</h3><p>A systematic search of Cochrane CENTRAL, Ovid Medline R, PubMed, and Web of Science databases up to March 1, 2024, was conducted. Randomized controlled trials (RCTs) directly comparing enarodustat with darbepoetin were included. Data from four unique RCTs comprising an inverse variance-weighted random-effects model were utilized for the main analysis. Primary efficacy outcome measures included hemoglobin (Hb) change at weeks 4-6 and during follow-up, while primary safety outcomes focused on serious adverse events (SAEs). Subgroup analyses were performed based on dialysis status and prior use of ESA for the primary outcome.</p></div><div><h3>Results</h3><p>Four RCTs with 7 reports involving 586 patients were included in the main analysis. Enarodustat demonstrated superiority to control in terms of change in Hb levels at week 4-6 (RR 0.76, 95% CI 0.02 to 1.50, I2=96%, p=0.04) but non-inferiority during follow-up (MD 0.66, 95% CI -0.22 to 1.53, I2=91%, p=0.14). Enarodustat exhibited comparable effects for safety and tolerability parameters such as SAEs (RR 1.17, 95% CI 0.72 to 1.91, I2=0%, p=0.52), any adverse events (RR 0.95, 95% CI 0.82 to 1.08), any adverse events leading to discontinuation (RR 0.90, 95% CI 0.37 to 2.20), diarrhea (RR 1.50, 95% CI 0.05 to 43.15), hypertension (RR 0.89, 95% CI 0.43 to 1.84), and all-cause mortality (RR 0.63, 95% CI 0.08 to 5.08). Subgroup analysis by dialysis status revealed nonsignificant differences for change in Hb levels at week 4-6 and during follow-up, but comparator-based subgroup analysis demonstrated a significant difference only when comparing to placebo at week 4-6.</p></div><div><h3>Conclusion</h3><p>Enarodustat exhibits promise as a treatment option for anemia associated with CKD, demonstrating superiority to control in terms of Hb change at week 4-6 and non-inferiority during follow-up. Moreover, it demonstrates comparable safety and tolerability profiles to darbepoetin, making it a potential alternative in the management of CKD-related anemia.</p></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2531137924000944/pdfft?md5=36b36a4ccc7d2a59cb04a9275032cfca&pid=1-s2.0-S2531137924000944-main.pdf","citationCount":"0","resultStr":"{\"title\":\"SHIFTING PARADIGMS: EXPLORING ENARODUSTAT FOR ANEMIA IN CHRONIC KIDNEY DISEASE IN A META ANALYSIS OF RANDOMIZED CONTROLLED TRIALS\",\"authors\":\"Lokman Hekim Tanrıverdi , Ahmet Sarıcı\",\"doi\":\"10.1016/j.htct.2024.04.012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Anemia commonly accompanies chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs), such as darbepoetin, are initiated for anemia in CKD. Additionally, hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors have demonstrated efficacy in treating CKD-associated anemia. This meta-analysis aims to compare the efficacy, safety, and tolerability of enarodustat in anemic CKD patients.</p><p><strong>Case report</strong></p></div><div><h3>Methodology</h3><p>A systematic search of Cochrane CENTRAL, Ovid Medline R, PubMed, and Web of Science databases up to March 1, 2024, was conducted. Randomized controlled trials (RCTs) directly comparing enarodustat with darbepoetin were included. Data from four unique RCTs comprising an inverse variance-weighted random-effects model were utilized for the main analysis. Primary efficacy outcome measures included hemoglobin (Hb) change at weeks 4-6 and during follow-up, while primary safety outcomes focused on serious adverse events (SAEs). Subgroup analyses were performed based on dialysis status and prior use of ESA for the primary outcome.</p></div><div><h3>Results</h3><p>Four RCTs with 7 reports involving 586 patients were included in the main analysis. Enarodustat demonstrated superiority to control in terms of change in Hb levels at week 4-6 (RR 0.76, 95% CI 0.02 to 1.50, I2=96%, p=0.04) but non-inferiority during follow-up (MD 0.66, 95% CI -0.22 to 1.53, I2=91%, p=0.14). Enarodustat exhibited comparable effects for safety and tolerability parameters such as SAEs (RR 1.17, 95% CI 0.72 to 1.91, I2=0%, p=0.52), any adverse events (RR 0.95, 95% CI 0.82 to 1.08), any adverse events leading to discontinuation (RR 0.90, 95% CI 0.37 to 2.20), diarrhea (RR 1.50, 95% CI 0.05 to 43.15), hypertension (RR 0.89, 95% CI 0.43 to 1.84), and all-cause mortality (RR 0.63, 95% CI 0.08 to 5.08). Subgroup analysis by dialysis status revealed nonsignificant differences for change in Hb levels at week 4-6 and during follow-up, but comparator-based subgroup analysis demonstrated a significant difference only when comparing to placebo at week 4-6.</p></div><div><h3>Conclusion</h3><p>Enarodustat exhibits promise as a treatment option for anemia associated with CKD, demonstrating superiority to control in terms of Hb change at week 4-6 and non-inferiority during follow-up. Moreover, it demonstrates comparable safety and tolerability profiles to darbepoetin, making it a potential alternative in the management of CKD-related anemia.</p></div>\",\"PeriodicalId\":12958,\"journal\":{\"name\":\"Hematology, Transfusion and Cell Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2531137924000944/pdfft?md5=36b36a4ccc7d2a59cb04a9275032cfca&pid=1-s2.0-S2531137924000944-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematology, Transfusion and Cell Therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2531137924000944\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology, Transfusion and Cell Therapy","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2531137924000944","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目标慢性肾脏病(CKD)常伴有贫血。促红细胞生成素(ESAs),如达贝泊汀,是治疗慢性肾脏病贫血的首选药物。此外,低氧诱导因子(HIF)脯氨酰羟化酶抑制剂对治疗 CKD 相关性贫血也有疗效。本荟萃分析旨在比较依那西普对贫血的 CKD 患者的疗效、安全性和耐受性。方法对截至 2024 年 3 月 1 日的 Cochrane CENTRAL、Ovid Medline R、PubMed 和 Web of Science 数据库进行了系统检索。研究纳入了直接比较依那曲达与达贝泊汀的随机对照试验(RCT)。主要分析采用了由反方差加权随机效应模型组成的四项独特 RCT 的数据。主要疗效结局指标包括第 4-6 周和随访期间的血红蛋白 (Hb) 变化,而主要安全性结局指标则侧重于严重不良事件 (SAE)。根据透析状态和先前使用ESA的主要结果进行了亚组分析。结果主要分析包括4项RCT和7份报告,涉及586名患者。就第4-6周的Hb水平变化而言,依那曲他优于对照组(RR为0.76,95% CI为0.02至1.50,I2=96%,P=0.04),但在随访期间无劣效(MD为0.66,95% CI为-0.22至1.53,I2=91%,P=0.14)。08)、导致停药的任何不良事件(RR 0.90,95% CI 0.37 至 2.20)、腹泻(RR 1.50,95% CI 0.05 至 43.15)、高血压(RR 0.89,95% CI 0.43 至 1.84)和全因死亡率(RR 0.63,95% CI 0.08 至 5.08)。按透析状态进行的亚组分析表明,第4-6周和随访期间的Hb水平变化无显著差异,但基于参照物的亚组分析表明,只有在第4-6周与安慰剂比较时才有显著差异。此外,它的安全性和耐受性也与达贝泊汀相当,因此有可能成为治疗慢性肾脏病相关贫血的替代药物。
SHIFTING PARADIGMS: EXPLORING ENARODUSTAT FOR ANEMIA IN CHRONIC KIDNEY DISEASE IN A META ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Objective
Anemia commonly accompanies chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs), such as darbepoetin, are initiated for anemia in CKD. Additionally, hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors have demonstrated efficacy in treating CKD-associated anemia. This meta-analysis aims to compare the efficacy, safety, and tolerability of enarodustat in anemic CKD patients.
Case report
Methodology
A systematic search of Cochrane CENTRAL, Ovid Medline R, PubMed, and Web of Science databases up to March 1, 2024, was conducted. Randomized controlled trials (RCTs) directly comparing enarodustat with darbepoetin were included. Data from four unique RCTs comprising an inverse variance-weighted random-effects model were utilized for the main analysis. Primary efficacy outcome measures included hemoglobin (Hb) change at weeks 4-6 and during follow-up, while primary safety outcomes focused on serious adverse events (SAEs). Subgroup analyses were performed based on dialysis status and prior use of ESA for the primary outcome.
Results
Four RCTs with 7 reports involving 586 patients were included in the main analysis. Enarodustat demonstrated superiority to control in terms of change in Hb levels at week 4-6 (RR 0.76, 95% CI 0.02 to 1.50, I2=96%, p=0.04) but non-inferiority during follow-up (MD 0.66, 95% CI -0.22 to 1.53, I2=91%, p=0.14). Enarodustat exhibited comparable effects for safety and tolerability parameters such as SAEs (RR 1.17, 95% CI 0.72 to 1.91, I2=0%, p=0.52), any adverse events (RR 0.95, 95% CI 0.82 to 1.08), any adverse events leading to discontinuation (RR 0.90, 95% CI 0.37 to 2.20), diarrhea (RR 1.50, 95% CI 0.05 to 43.15), hypertension (RR 0.89, 95% CI 0.43 to 1.84), and all-cause mortality (RR 0.63, 95% CI 0.08 to 5.08). Subgroup analysis by dialysis status revealed nonsignificant differences for change in Hb levels at week 4-6 and during follow-up, but comparator-based subgroup analysis demonstrated a significant difference only when comparing to placebo at week 4-6.
Conclusion
Enarodustat exhibits promise as a treatment option for anemia associated with CKD, demonstrating superiority to control in terms of Hb change at week 4-6 and non-inferiority during follow-up. Moreover, it demonstrates comparable safety and tolerability profiles to darbepoetin, making it a potential alternative in the management of CKD-related anemia.