Department of Nephrology, Wakayama Medical University, Wakayama, Japan.
Medical Affairs Department, Kyowa Kirin Co., Ltd., Tokyo, Japan.
PLoS One. 2022 Feb 17;17(2):e0262829. doi: 10.1371/journal.pone.0262829. eCollection 2022.
This ad hoc analysis of a previously conducted phase 3 head-to-head comparison study of evocalcet and cinacalcet in secondary hyperparathyroidism patients undergoing maintenance hemodialysis evaluated the efficacy and safety of combined once-daily oral evocalcet and intravenous vitamin D receptor activator treatment stratified by weekly vitamin D receptor activator dose (117, 45, and 91 patients in no, low [< 1.5 μg], and high [≥ 1.5 μg] dose groups, respectively). Effects of vitamin D receptor activator were assessed on the basis of intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels; percent changes from baseline; proportions of patients who achieved target intact parathyroid hormone, corrected calcium, and phosphorus at Weeks 28-30; and adverse drug reactions. Intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels decreased in all groups; phosphorus and fibroblast growth factor-23 levels remained high in the high dose group. In the low and high dose groups, greater proportions of patients achieved the corrected calcium target compared with the no dose group (p = 0.043). Ratios of intact-to-C-terminal fibroblast growth factor-23 decreased in all groups. In low and high dose groups, hypocalcemia was less common than in the no dose group (p = 0.014). Evocalcet with concomitant vitamin D receptor activator demonstrated benefits such that more patients achieved the corrected calcium target and exhibited decreased fibroblast growth factor-23 synthesis; the incidence of hypocalcemia also decreased. Clinical trial registration: ClinicalTrials.gov (NCT02549391) and JAPIC (JapicCTI-153013).
这项针对接受维持性血液透析的继发性甲状旁腺功能亢进症患者的依卡路肽与西那卡塞头对头 3 期对比研究的事后分析,评估了联合每日一次口服依卡路肽与静脉用维生素 D 受体激动剂治疗的疗效和安全性,该研究按每周维生素 D 受体激动剂剂量分层(无剂量组、低剂量[<1.5μg]组和高剂量[≥1.5μg]组分别有 117、45 和 91 例患者)。根据全段甲状旁腺激素、校正钙、磷和成纤维细胞生长因子 23 水平、自基线的变化百分比、28-30 周时达到目标全段甲状旁腺激素、校正钙和磷的患者比例以及药物不良反应评估维生素 D 受体激动剂的作用。所有组的全段甲状旁腺激素、校正钙、磷和成纤维细胞生长因子 23 水平均降低;高剂量组的磷和成纤维细胞生长因子 23 水平仍较高。在低剂量和高剂量组中,与无剂量组相比,更多的患者达到了校正钙的目标(p=0.043)。所有组的全段与 C 端成纤维细胞生长因子 23 的比值均降低。在低剂量和高剂量组中,与无剂量组相比,低钙血症的发生率较低(p=0.014)。依卡路肽联合维生素 D 受体激动剂具有益处,更多的患者达到了校正钙的目标,并且成纤维细胞生长因子 23 的合成减少;低钙血症的发生率也降低。临床试验注册:ClinicalTrials.gov(NCT02549391)和 Japic(JapicCTI-153013)。