罗沙司他与红细胞生成刺激剂治疗非透析依赖或透析相关慢性肾脏病贫血患者的安全性：四项 3 期研究的汇总分析。
Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies.
机构信息
Department of Cardiovascular Sciences, University of Leicester, University Rd, Leicester, LE1 7RH, UK.
Department of Nephrology and Dialysis, MVZ DaVita Rhein-Ruhr GmbH, Düsseldorf, Germany.
出版信息
Adv Ther. 2023 Apr;40(4):1546-1559. doi: 10.1007/s12325-023-02433-0. Epub 2023 Feb 7.
INTRODUCTION
This study was conducted to elucidate the safety of roxadustat, an oral medication, in patients with non-dialysis-dependent (NDD) or incident dialysis dialysis-dependent (ID-DD) chronic kidney disease (CKD).
METHODS
Safety results from four phase 3, randomized, open-label studies comparing roxadustat to an erythropoiesis-stimulating agent (ESA) in men and women with NDD or ID-DD CKD with anemia were pooled and evaluated. Endpoints were time to major adverse cardiovascular event (MACE; myocardial infarction, stroke, and all-cause mortality) and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), all-cause mortality, and treatment-emergent adverse events (TEAEs). MACE and MACE+ were evaluated for non-inferiority at 1.8- and 1.3-margins using hazard ratios (HRs) and 95% confidence intervals (CIs). TEAEs were descriptively summarized.
RESULTS
In total, 2142 patients were evaluated (1083 roxadustat; 1059 ESA). Roxadustat was comparable to ESA for risk of MACE (HR 0.79, 95% CI 0.61-1.02), MACE+ (HR 0.78, 95% CI 0.62-0.98), and all-cause mortality (HR 0.78, 95% CI 0.57-1.05). TEAEs were comparable between roxadustat and ESA groups, including any TEAE [incidence rate per 100 (IR/100) patient-exposure years 56.1 vs. 53.5], TEAEs leading to study drug discontinuation (IR/100 patient-exposure years 6.7 vs. 5.1), and TEAEs leading to death (IR/100 patient-exposure years 6.9 vs. 7.4).
CONCLUSION
There was no evidence of increased risk of cardiovascular events or mortality with roxadustat compared with ESA in patients with anemia who have NDD or ID-DD CKD. Although TEAEs occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued the study drug because of an adverse event.
CLINICAL TRIAL REGISTRATION NUMBERS
DOLOMITES, 1517-CL-0610 [NCT02021318]; HIMALAYAS, FGCL-4592-063 [NCT02052310]; SIERRAS, FGCL-4592-064 [NCT02273726]; and ROCKIES, D5740C00002 [NCT02174731].
简介
本研究旨在阐明罗沙司他作为一种口服药物在非透析依赖型（NDD）或起始透析依赖型（ID-DD）慢性肾脏病（CKD）患者中的安全性。
方法
对四项比较罗沙司他与红细胞生成刺激剂（ESA）在 NDD 或 ID-DD CKD 伴贫血的男性和女性中的疗效的 3 期、随机、开放标签研究的安全性结果进行了汇总和评估。终点为主要不良心血管事件（MACE；心肌梗死、卒中和全因死亡率）和 MACE+（MACE 加充血性心力衰竭或需要住院的不稳定型心绞痛）、全因死亡率和治疗中出现的不良事件（TEAEs）。使用风险比（HR）和 95%置信区间（CI），以 1.8 和 1.3 的边界评估 MACE 和 MACE+的非劣效性。TEAEs 采用描述性方法进行总结。
结果
共有 2142 例患者接受了评估（罗沙司他 1083 例，ESA 1059 例）。罗沙司他与 ESA 相比，MACE 的风险相当（HR 0.79，95%CI 0.61-1.02），MACE+（HR 0.78，95%CI 0.62-0.98）和全因死亡率（HR 0.78，95%CI 0.57-1.05）。罗沙司他和 ESA 组的 TEAEs 相当，包括任何 TEAE[每 100 例患者暴露年发生率（IR/100）56.1 比 53.5]、导致研究药物停药的 TEAE（IR/100 患者暴露年发生率 6.7 比 5.1）和导致死亡的 TEAE（IR/100 患者暴露年发生率 6.9 比 7.4）。
结论
与 ESA 相比，罗沙司他在 NDD 或 ID-DD CKD 伴贫血的患者中并未增加心血管事件或死亡的风险。尽管罗沙司他和 ESA 组均常发生 TEAEs，但因不良事件而停药的患者很少。
临床试验注册号
DOLOMITES，1517-CL-0610[NCT02021318]；HIMALAYAS，FGCL-4592-063[NCT02052310]；SIERRAS，FGCL-4592-064[NCT02273726]；和 ROCKIES，D5740C00002[NCT02174731]。
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