盐酸西那卡塞对日本继发性甲状旁腺功能亢进血液透析患者的长期疗效及安全性：开放标签52周研究
Long-Term Efficacy and Safety of Upacicalcet in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism: Open-Label 52-Week Study.
作者信息
Hamano Takayuki, Koiwa Fumihiko, Isaka Yoshitaka, Yokoyama Keitaro, Fukagawa Masafumi, Inagaki Yosuke, Watanabe Yukihisa S, Honda Daisuke, Akizawa Tadao
机构信息
Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
出版信息
Am J Nephrol. 2025;56(1):70-84. doi: 10.1159/000541493. Epub 2024 Sep 19.
INTRODUCTION
Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT).
METHODS
Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Upacicalcet with a dose range of 25-300 µg was administered after each dialysis for 52 weeks. The main efficacy endpoint was the percentage of patients achieving the target iPTH level (60-240 pg/mL).
RESULTS
A total of 157 patients were enrolled, of whom 138 completed the study. Overall, 94.2% of patients achieved the target serum iPTH level at week 52. Neither symptomatic hypocalcemia nor cCa level <7.5 mg/dL occurred despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Upacicalcet improved the control of serum phosphate (P) and calcium levels regardless of baseline PTH levels and decreased intact fibroblast growth factor-23 levels. The largest parathyroid glands shrank, irrespective of their baseline volume or prior calcimimetic usage. Upacicalcet was well tolerated, with no adverse events requiring dose reduction.
CONCLUSION
This is the first study to show that a calcimimetic improves serum P and cCa control without inducing severe hypocalcemia in patients with iPTH levels ≤300 pg/mL. Upacicalcet is efficacious in HD patients with mild-to-severe SHPT, with few safety concerns.
INTRODUCTION
Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT).
METHODS
Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Upacicalcet with a dose range of 25-300 µg was administered after each dialysis for 52 weeks. The main efficacy endpoint was the percentage of patients achieving the target iPTH level (60-240 pg/mL).
RESULTS
A total of 157 patients were enrolled, of whom 138 completed the study. Overall, 94.2% of patients achieved the target serum iPTH level at week 52. Neither symptomatic hypocalcemia nor cCa level <7.5 mg/dL occurred despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Upacicalcet improved the control of serum phosphate (P) and calcium levels regardless of baseline PTH levels and decreased intact fibroblast growth factor-23 levels. The largest parathyroid glands shrank, irrespective of their baseline volume or prior calcimimetic usage. Upacicalcet was well tolerated, with no adverse events requiring dose reduction.
CONCLUSION
This is the first study to show that a calcimimetic improves serum P and cCa control without inducing severe hypocalcemia in patients with iPTH levels ≤300 pg/mL. Upacicalcet is efficacious in HD patients with mild-to-severe SHPT, with few safety concerns.
引言
upacicalcet是一种新型注射用拟钙剂。这项3期多中心开放标签研究旨在评估upacicalcet在继发性甲状旁腺功能亢进（SHPT）的血液透析（HD）患者中的长期疗效和安全性。
方法
纳入血清完整甲状旁腺激素（iPTH）水平>240 pg/mL且校正钙（cCa）水平≥8.4 mg/dL的日本HD患者。每次透析后给予剂量范围为25 - 300 µg的upacicalcet，持续52周。主要疗效终点是达到目标iPTH水平（60 - 240 pg/mL）的患者百分比。
结果
共纳入157例患者，其中138例完成研究。总体而言，94.2%的患者在第52周时达到目标血清iPTH水平。尽管同时使用的维生素D受体激活剂和碳酸钙增加量可忽略不计，但未发生症状性低钙血症，cCa水平也未<7.5 mg/dL。无论基线PTH水平如何，upacicalcet均改善了血清磷酸盐（P）和钙水平的控制，并降低了完整成纤维细胞生长因子23水平。最大的甲状旁腺缩小，无论其基线体积或先前拟钙剂的使用情况如何。Upacicalcet耐受性良好，无需要减少剂量的不良事件。
结论
这是第一项表明拟钙剂可改善血清P和cCa控制且不会在iPTH水平≤300 pg/mL的患者中诱发严重低钙血症的研究。Upacicalcet对轻至重度SHPT的HD患者有效，安全性担忧较少。
引言
upacicalcet是一种新型注射用拟钙剂。这项3期多中心开放标签研究旨在评估upacicalcet在继发性甲状旁腺功能亢进（SHPT）的血液透析（HD）患者中的长期疗效和安全性。
方法
纳入血清完整甲状旁腺激素（iPTH）水平>240 pg/mL且校正钙（cCa）水平≥8.4 mg/dL的日本HD患者。每次透析后给予剂量范围为25 - 300 µg的upacicalcet，持续52周。主要疗效终点是达到目标iPTH水平（60 - 240 pg/mL）的患者百分比。
结果
共纳入157例患者，其中138例完成研究。总体而言，94.2%的患者在第52周时达到目标血清iPTH水平。尽管同时使用的维生素D受体激活剂和碳酸钙增加量可忽略不计，但未发生症状性低钙血症，cCa水平也未<7.5 mg/dL。无论基线PTH水平如何，upacicalcet均改善了血清磷酸盐（P）和钙水平的控制，并降低了完整成纤维细胞生长因子23水平。最大的甲状旁腺缩小，无论其基线体积或先前拟钙剂的使用情况如何。Upacicalcet耐受性良好，无需要减少剂量的不良事件。
结论
这是第一项表明拟钙剂可改善血清P和cCa控制且不会在iPTH水平≤300 pg/mL的患者中诱发严重低钙血症的研究。Upacicalcet对轻至重度SHPT的HD患者有效，安全性担忧较少。
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