Nangaku Masaomi, Kondo Kazuoki, Kokado Yoshimasa, Ueta Kiichiro, Kaneko Genki, Tandai Tsubasa, Kawaguchi Yutaka, Komatsu Yasuhiro
Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
J Am Soc Nephrol. 2021 Jul;32(7):1779-1790. doi: 10.1681/ASN.2020091311. Epub 2021 Apr 21.
Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo.
In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety data included adverse events (AEs) and serious AEs.
A total of 151 participants received vadadustat and 153 received darbepoetin alfa. Least squares mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit for the difference between groups (-0.50 g/dl) was above the predefined noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to darbepoetin alfa. Similar proportions of patients in each group reported AEs and serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, diarrhea, and constipation.
In Japanese patients with NDD-CKD, vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in terms of average hemoglobin, and was generally well tolerated. These results suggest that vadadustat may be a potential treatment for anemia in this patient population.
治疗慢性肾脏病（CKD）患者贫血的标准护理措施包括使用促红细胞生成素，这有时会增加心血管疾病发病率和死亡率的风险。先前针对贫血且非透析依赖型CKD（NDD-CKD）患者的研究发现，与安慰剂相比，使用口服低氧诱导因子脯氨酰羟化酶抑制剂瓦达他司他可显著提高血红蛋白水平。
在这项3期、开放标签、活性对照非劣效性试验中，我们将304名患有NDD-CKD贫血的日本成年人（包括使用和未使用促红细胞生成素的患者）随机分为口服瓦达他司他组或皮下注射阿法依泊汀组，治疗52周。主要疗效终点是第20周和第24周时的平均血红蛋白水平。安全性数据包括不良事件（AE）和严重不良事件。
共有151名参与者接受了瓦达他司他治疗，153名接受了阿法依泊汀治疗。瓦达他司他组在第20周和第24周时平均血红蛋白的最小二乘均值为11.66（95%置信区间[95%CI]，11.49至11.84）g/dl，阿法依泊汀组为11.93（95%CI，11.76至12.10）g/dl。两种治疗的95%CI均在目标血红蛋白范围内（11.0 - 13.0 g/dl），且两组差异的95%置信下限（-0.50 g/dl）高于预先定义的非劣效界值（-0.75 g/dl），表明瓦达他司他不劣于阿法依泊汀。每组报告AE和严重AE的患者比例相似。瓦达他司他最常见的AE是鼻咽炎、腹泻和便秘。
在日本NDD-CKD患者中，瓦达他司他不劣于阿法依泊汀，在第52周时平均血红蛋白水平方面有效，且总体耐受性良好。这些结果表明，瓦达他司他可能是该患者群体贫血的一种潜在治疗方法。
