California Institute of Renal Research, San Diego, California, USA.
Renal Transplant Associates of New England, Springfield, Massachusetts, USA.
Am J Nephrol. 2021;52(10-11):798-807. doi: 10.1159/000518545. Epub 2021 Oct 27.
The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee®) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC's efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population.
Medical records of 174 patients who met study criteria from 15 geographically representative United States nephrology clinics were reviewed for 1 year before and after initiation of ERC treatment. Enrolled subjects had ages ≥18 years, stage 3 or 4 CKD, and a history of SHPT and VDI. Key study variables included patient demographics, medication usage, and laboratory results, including serial 25D and PTH determinations.
The enrolled subjects had a mean age of 69.0 years, gender and racial distributions representative of the indicated population, and were balanced for CKD stage. Most (98%) received 30 mcg of ERC/day during the course of treatment (mean follow-up: 24 weeks). Baseline 25D and PTH levels averaged 20.3 ± 0.7 (standard error) ng/mL and 181 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (p < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL (p < 0.001) with nominal changes of 0.1 mg/dL (p > 0.05) in serum calcium (Ca) and phosphorus (P) levels.
DISCUSSION/CONCLUSION: Analysis of postlaunch data confirmed ERC's effectiveness in increasing serum 25D and reducing PTH levels without statistically significant or notable impact on serum Ca and P levels. A significant percentage of these subjects achieved 25D levels ≥30 mg/mL and PTH levels which decreased by at least 30% from baseline. Dose titration to 60 mcgs was rarely prescribed. Closer patient monitoring and appropriate dose titration may have led to a higher percentage of subjects achieving an increase in 25D levels to at least 50 ng/mL and a reduction in PTH levels of at least 30%.
在患有 3 或 4 期慢性肾脏病（CKD）和维生素 D 不足（VDI）的成人中，延长释放型 calcifediol（ERC）作为治疗继发性甲状旁腺功能亢进症（SHPT）的安全性和有效性已在前瞻性随机临床试验（RCT）中得到证实。ERC（Rayaldee®）基于这些前瞻性 RCT，于 2016 年获得美国食品和药物管理局的批准。目前，这项回顾性研究评估了 ERC 在增加血清 25-羟维生素 D（25D）和降低指示人群甲状旁腺激素（PTH）方面的上市后数据的疗效和安全性。
从 15 个具有地理代表性的美国肾脏病诊所中，对符合研究标准的 174 名患者的病历进行了回顾性研究，评估了他们在开始 ERC 治疗前和治疗后的 1 年。入选的患者年龄≥18 岁，患有 3 或 4 期 CKD，并有 SHPT 和 VDI 病史。主要研究变量包括患者的人口统计学、药物使用情况以及实验室结果，包括连续 25D 和 PTH 测定。
入选的患者平均年龄为 69.0 岁，性别和种族分布与指示人群相符，CKD 分期平衡。大多数（98%）患者在治疗过程中接受 30 mcg/天的 ERC（平均随访：24 周）。基线 25D 和 PTH 水平分别平均为 20.3±0.7（标准误差）ng/mL 和 181±7.4 pg/mL。ERC 治疗使 25D 升高 23.7±1.6 ng/mL（p<0.001），PTH 降低 34.1±6.6 pg/mL（p<0.001），血清钙（Ca）和磷（P）水平的变化为 0.1 mg/dL（p>0.05）。
讨论/结论：上市后数据分析证实，ERC 可有效增加血清 25D 并降低 PTH 水平，对血清 Ca 和 P 水平无统计学显著或明显影响。这些患者中有很大一部分达到了 25D 水平≥30mg/mL 和 PTH 水平降低至少 30%基线值。很少开 60mcg 剂量的处方。更密切的患者监测和适当的剂量调整可能会使更多的患者达到至少 50ng/mL 的 25D 水平增加和至少 30%的 PTH 水平降低。
