慢性肾脏病贫血患者使用莫立司他的长期疗效和安全性：DIALOGUE 扩展研究。
Long-Term Efficacy and Safety of Molidustat for Anemia in Chronic Kidney Disease: DIALOGUE Extension Studies.
机构信息
Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Department of Renal Medicine, King's College Hospital, London, United Kingdom.
出版信息
Am J Nephrol. 2019;49(4):271-280. doi: 10.1159/000499111. Epub 2019 Mar 8.
BACKGROUND
Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat.
METHODS
Both studies were parallel-group, open-label, multicenter studies of ≤36 months' duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control. One study enrolled patients not receiving dialysis (n = 164), and the other enrolled patients receiving hemodialysis (n = 88). The primary efficacy variable for both studies was change in blood hemoglobin (Hb) level from baseline to each post-baseline visit, and safety outcomes included adverse events (AEs).
RESULTS
In patients not on dialysis, the mean ± SD Hb concentrations at baseline were 11.28 ± 0.55 g/dL for molidustat and 11.08 ± 0.51 g/dL for darbepoetin. The mean ± SD blood Hb concentrations throughout the study (defined as mean of each patient's overall study Hb levels) were 11.10 ± 0.508 and 10.98 ± 0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. Similar proportions of patients reported at least one AE in the molidustat (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean ± SD Hb levels at baseline were 10.40 ± 0.70 and 10.52 ± 0.53 g/dL in the molidustat and epoetin groups, respectively. The mean ± SD blood Hb concentrations during the study were 10.37 ± 0.56 g/dL in the molidustat group and 10.52 ± 0.47 g/dL in the epoetin group. Proportions of patients who reported at least one AE were 91.2% in the molidustat group and 93.3% in the epoetin group.
CONCLUSIONS
Molidustat was well tolerated for up to 36 months and appears to be an effective alternative to darbepoetin and epoetin in the long-term management of anemia associated with CKD.
背景
莫利司他是一种新型低氧诱导因子脯氨酰羟化酶抑制剂，目前正在进行治疗慢性肾脏病（CKD）相关贫血的临床试验。最近有三项为期 16 周的 2b 期临床试验评估了莫利司他的疗效和安全性。在此，我们报告了两项莫利司他长期扩展研究的结果。
方法
这两项研究均为非透析（n=164）和透析（n=88）患者的平行分组、开放标签、多中心研究，研究时间均不超过 36 个月，研究药物均为红细胞生成刺激剂。主要疗效变量是从基线到每次随访时的血血红蛋白（Hb）水平变化，安全性结局包括不良事件（AE）。
结果
在非透析患者中，莫利司他和达贝泊汀的基线平均±标准差 Hb 浓度分别为 11.28±0.55g/dL 和 11.08±0.51g/dL。整个研究期间的平均±标准差血 Hb 浓度（定义为每位患者的总体研究 Hb 水平的平均值）在莫利司他组和达贝泊汀组分别为 11.10±0.508 和 10.98±0.571g/dL。莫利司他组（85.6%）和达贝泊汀组（85.7%）报告至少一次 AE 的患者比例相似。在透析患者中，莫利司他和 epoetin 组的基线平均±标准差 Hb 水平分别为 10.40±0.70 和 10.52±0.53g/dL。研究期间的平均±标准差血 Hb 浓度分别为莫利司他组 10.37±0.56g/dL 和 epoetin 组 10.52±0.47g/dL。报告至少一次 AE 的患者比例分别为莫利司他组 91.2%和 epoetin 组 93.3%。
结论
莫利司他耐受良好，最长可使用 36 个月，似乎是 CKD 相关贫血长期治疗中达贝泊汀和 epoetin 的有效替代药物。
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