Health-economic comparison of paricalcitol, calcitriol and alfacalcidol for the treatment of secondary hyperparathyroidism during haemodialysis

This study evaluated the health-economic consequences of use of intravenous paricalcitol (Zemplar), oral calcitriol or oral and intravenous alfacalcidol for the treatment of patients with secondary hyperparathyroidism, focusing on a third-party payer perspective through inclusion of medication and hospital costs, survival rates and utilities. Cost values were based on German treatment recommendations and prices. Reference values for survival rates and utilities were based on the results of a MEDLINE search. The analysis showed a clear advantage for intravenous paricalcitol with respect to costs, effectiveness and utilities compared with treatment with oral calcitriol or intravenous alfacalcidol. Since the results were very cost sensitive with respect to selected diagnosis-related groups (DRGs) for kidney disease with dialysis, a sensitivity analysis was performed. This demonstrated first-order dominance of intravenous paricalcitol for a wide range of hospitalisation costs. In conclusion, this analysis suggested a clear benefit from the perspective of a third-party payer for intravenous paricalcitol compared with oral calcitriol and intravenous alfacalcidol in the treatment of patients with secondary hyperparathyroidism.     

骨化三醇治疗慢性肾脏病继发性甲状旁腺功能亢进的疗效

目的探讨骨化三醇冲击治疗慢性肾脏病继发性甲状旁腺功能亢进的临床疗效。方法根据血清全段甲状旁腺激素(iPTH)水平选择尚未进入替代治疗的慢性肾脏病(CKD 4、5期)65例,比较治疗前及治疗后4、8、12周的iPTH、血钙、血磷的变化及临床症状的缓解情况。结果 65例患者经治疗12周后,血清iPTH水平明显下降,与治疗前比较差异具有统计学意义(P<0.05)。患者的血钙较治疗前有上升趋势,而血磷有下降趋势。在治疗8、12周时,患者的Ca2+×P3-明显低于治疗前,差异具有统计学意义(P<0.05)。临床症状有不同程度改善,72.3%患者症状明显改善。结论骨化三醇口服治疗慢性肾脏病合并继发性甲状旁腺功能亢进的非透析患者疗效显著,临床症状改善明显。     

伊特卡赛肽:治疗慢性肾病继发性甲状旁腺机能亢进新药

伊特卡赛肽（商品名为Parsabiv^TM）是安进公司开发的新型二代拟钙剂,主要用于治疗慢性肾病继发性甲状旁腺机能亢进。伊特卡赛肽通过直接与钙感应受体结合来降低血钙浓度,还可以降低甲状旁腺素的水平。欧盟于2016年11月批准注射用伊特卡赛肽用于慢性肾病继发性甲状旁腺机能亢进的透析患者。介绍该药的药理作用、药动学、临床试验及不良反应研究概况。     

Calcifediol to treat secondary hyperparathyroidism in patients with chronic kidney disease

Introduction: Deranged vitamin D metabolism represents an active trigger of secondary hyperparathyroidism (SHPT) in CKD. Correction of 25(OH)D deficiency by nutritional Vitamin D administration is suggested by KDIGO guidelines, to prevent and treat SHPT in CKD stage G3-G5 and G1T-G5T patients, although with a still inconsistent background. Nutritional vitamin D is available as cholecalciferol, ergocalciferol, or calcifediol. Superiority of calcifediol in increasing 25(OH)D levels has been suggested due to its better bioavailability. The safer pharmacokinetic of the recent modified-release (MR) formulation of calcifediol was effective in replenishing 25(OH)D levels with minimal impact on vitamin D catabolism and fibroblast-growth factor-23 (FGF-23) activation.

Areas covered: the review discusses utility of calcifediol for treating SHPT in different CKD stages under physiology driven approach, focusing on vitamin D metabolism, guidelines suggestions and comparison between clinical effects on SHPT elicited by calcifediol, cholecalciferol and ergocalciferol.

Expert commentary: although optimal targets of 25(OH)D and parathormone remain uncertain, calcifediol, especially in its newer MR formulation, may represent an intriguing option to combine an efficacious correction of 25(OH)D deficit and SHPT, with a limited impact on vitamin D catabolism and FGF-23 activation. Newer data are required to better explore the role of MR calcifediol in treating SHPT.     

Pathogenesis and treatment of secondary hyperparathyroidism in dialysis patients: the role of paricalcitol

Hemodialysis (HD) patients are commonly affected by secondary hyperparathyroidism (SHPT), in which 3 well-known factors are usually involved: hypocalcemia, hyperphosphatemia and calcitriol deficiency. Classically, high parathyroid hormone (PTH) levels cause bone-associated diseases, such as osteitis fibrosa and renal osteodystrophy, but more recently it has been demonstrated the link between SHPT and a systemic toxicity, with a major role in determining cardio-vascular disease, including arterial calcification, endocrine disturbances, compromised immune system, neurobehavioral changes, and altered erythropoiesis. Treatment with calcitriol (CT), the active form of vitamin D, reduces parathyroid hormone (PTH) levels, but may result in elevations in serum calcium (Ca) and phosphorus (P), increasing the risk of cardio-vascular calcification in the HD population. Several new vitamin D analogs have been developed and investigated with the rationale to treat SHPT with a reduced risk of hypercalcemia and hyperphosphatemia in HD patients. Paricalcitol (1,25-dihydroxy-19-nor-vitamin D(2), 19-Nor-D(2)) is a vitamin D analog that suppresses PTH secretion with minimal increases on serum calcium and phosphate levels. It was demonstrated that paricalcitol prevents vascular calcification in experimental models of renal failure, compared with calcitriol. Furthermore, 19-Nor-D(2) is the first analog approved for use in HD patients and is available for i.v. and oral administration, commonly 3 times weekly after HD. The purpose of the present review is to analyze the pathogenesis and treatment of SHPT in HD patients, and the role of paricalcitol in the prevention of arterial calcification.     

Paricalcitol capsules for the control of secondary hyperparathyroidism in chronic kidney disease

Secondary hyperparathyroidism is a common complication of patients with chronic kidney disease. Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus. New vitamin D analogues have been developed to reduce parathyroid hormone secretion without concomitant hypercalcaemia and hyperphosphataemia. Recent data from studies with paricalcitol capsules, the oral formulation of 19-nor-1,25(OH)2D2, show a significant reduction in parathyroid hormone levels with no change in calcium and phosphorus levels when compared with placebo. Paricalcitol also compares favourably to other oral vitamin D analogues, effectively decreasing parathyroid secretion with less hypercalcaemia and hypercalciuria than other agents.     

Paricalcitol capsules for the control of secondary hyperparathyroidism in chronic kidney disease

Secondary hyperparathyroidism is a common complication of patients with chronic kidney disease. Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus. New vitamin D analogues have been developed to reduce parathyroid hormone secretion without concomitant hypercalcaemia and hyperphosphataemia. Recent data from studies with paricalcitol capsules, the oral formulation of 19-nor-1,25(OH)₂D₂, show a significant reduction in parathyroid hormone levels with no change in calcium and phosphorus levels when compared with placebo. Paricalcitol also compares favourably to other oral vitamin D analogues, effectively decreasing parathyroid secretion with less hypercalcaemia and hypercalciuria than other agents.     

西那卡塞联合帕立骨化醇治疗血液透析患者继发性甲状旁腺功能亢进的疗效与安全性

目的观察西那卡塞联合帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺功能亢进症(Secondary hyperparathyroidism,SHPT)的疗效及安全性。方法选择我科血液净化中心进行维持性治疗的19例患者,血全段甲状旁腺素(Intact parathyroid hormone,iPTH)≥600 pg/mL,根据iPTH水平使用帕立骨化醇和西那卡塞治疗,共观察12周。分别于治疗前及治疗后第2、4、8、12周测定患者的iPTH、血钙、血磷、碱性磷酸酶(Alkaline phosphatase,AKP)水平。结果治疗后第2周,19例患者的血清iPTH水平开始下降,但差异无统计学意义(P>0.05)。从治疗后第4周开始,iPTH水平与治疗前比较差异有统计学意义(P<0.05);治疗后第12周时,下降至(841.78±730.17)pg/mL。治疗后,血钙水平显著降低(P<0.05)。治疗前后AKP、血磷、钙磷乘积水平比较差异无统计学意义(P>0.05)。治疗过程中,患者耐受性良好。结论西那卡塞联合帕立骨化醇治疗维持性血液透析患者SHPT安全、有效。     

慢性肾脏病继发甲状旁腺功能亢进的手术治疗

继发性甲状旁腺功能亢进（SHPT）是慢性肾脏病（CKD）的常见并发症，生理上以甲状旁腺激素过度合成和分泌、甲状旁腺细胞过度增生为特点，引起心肌、皮肤、骨骼、造血系统及脂质代谢等多系统病变，严重影响CKD患者生活质量。本文综合国内外文献对SHPT的发病机制、手术治疗、介入治疗的现状进行总结，旨在增加对慢性肾脏病继发甲状旁腺功能亢进症（CKD-SHPT）的认识，提高CKD患者生活质量，更好地完成对SHPT疾病的诊治工作。     

Medical therapy of secondary hyperparathyroidism in chronic kidney disease: old and new drugs

Secondary hyperparathyroidism (SHPT), a common complication of chronic kidney disease, is characterised by elevated serum levels of parathyroid hormone, parathyroid hyperplasia, excessive bone resorption and increased risk for cardiovascular morbidity. The stringent metabolic targets proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) for patients with SHPT are difficult to achieve using conventional treatment regimens. Several new agents, including new vitamin D sterols and phosphate binders, as well as a novel class of compounds – the calcimimetics – have been developed in recent years. This review examines new and traditional therapies for SHPT and how these can best be utilised in order to achieve the new K/DOQI targets.     

Medical therapy of secondary hyperparathyroidism in chronic kidney disease: old and new drugs

Secondary hyperparathyroidism (SHPT), a common complication of chronic kidney disease, is characterised by elevated serum levels of parathyroid hormone, parathyroid hyperplasia, excessive bone resorption and increased risk for cardiovascular morbidity. The stringent metabolic targets proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) for patients with SHPT are difficult to achieve using conventional treatment regimens. Several new agents, including new vitamin D sterols and phosphate binders, as well as a novel class of compounds--the calcimimetics--have been developed in recent years. This review examines new and traditional therapies for SHPT and how these can best be utilised in order to achieve the new K/DOQI targets.     

慢性肾脏病继发甲状旁腺功能亢进症50例临床分析

目的探讨慢性肾脏病(CKD)合并继发性甲状旁腺功能亢进症(SHPT)患者血清甲状旁腺激素(PTH)、钙磷水平的变化及其治疗对策。方法 50例CKD合并SHPT患者随机分为治疗组(30例)和对照组(20例),对照组采用常规治疗,治疗组在对照组基础上加用骨化三醇、磷结合剂及低钙透析液治疗。检测两组血清PTH、血清碱性磷酸酶(ALP)、血清钙、磷浓度,计算钙磷乘积。结果与对照组和治疗前相比,治疗组治疗期间的PTH、ALP水平和钙磷乘积下降(P<0.05),治疗20周后心血管疾患、感染、肾性骨病、贫血等并发症减少(P<0.05)。结论积极调整CKD患者钙磷代谢及血清PTH、ALP水平,对减少CKD患者并发症有重要意义。     

Clinical analysis on 50 chroic kidney disease patients complicated with secondary hyperparathyroidism

目的 探讨慢性肾脏病(CKD)合并继发性甲状旁腺功能亢进症(SHPT)患者血清甲状旁腺激素( PTH)、钙磷水平的变化及其治疗对策.方法 50例CKD合并SHPT患者随机分为治疗组(30例)和对照组(20例),对照组采用常规治疗,治疗组在对照组基础上加用骨化三醇、磷结合剂及低钙透析液治疗.检测两组血清PTH、血清碱性磷酸酶(ALP)、血清钙、磷浓度,计算钙磷乘积.结果 与对照组和治疗前相比,治疗组治疗期间的PTH、ALP水平和钙磷乘积下降(P＜0.05),治疗20周后心血管疾患、感染、肾性骨病、贫血等并发症减少(P＜0.05).结论 积极调整CKD患者钙磷代谢及血清PTH、ALP水平,对减少CKD患者并发症有重要意义.     

西那卡塞片联合骨化三醇胶囊治疗肾病患者中的甲状旁腺功能亢进的临床研究

目的观察西那卡塞片联合骨化三醇胶囊治疗肾病患者中的甲状旁腺功能亢进(UHPT)的临床疗效和安全性。方法将82例慢性透析而致的中重度UHPT病患者随机分为对照组41例和试验组41例。对照组予以骨化三醇,初始剂量为0.25μg,若患者能耐受,则将剂量调节至0.5μg,qd,口服;试验组在对照组治疗基础上加用西那卡塞25 mg,qd,口服。2组均治疗3个月。比较2组患者的临床疗效、全段甲状旁腺激素(iP TH)、碱性磷酸酶(ALP)、磷(P)、钙(Ca)和药物不良反应发生率。结果治疗后,试验组和对照组的总有效率分别为93.00%(38例/41例)和71.00%(29例/41例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的iP TH分别为(218.61±19.77),(323.50±32.72)ng·L^-1;ALP分别为(73.55±6.89),(118.79±11.70)U·L^-1;P分别为(1.32±0.12)mmol·L^-1和(1.59±0.14)mmol·L^-1,Ca分别为(2.77±0.36)mmol·L^-1和(2.33±0.28)mmol·L^-1,差异均有统计学意义(均P<0.05)。2组患者的药物不良反应为高血压、肌痛和恶心呕吐,试验组和对照组的药物不良反应发生率分别为12.00%(5例/41例)和15.00%(6例/41例),差异无统计学意义(P>0.05)。结论西那卡塞片联合骨化三醇胶囊治疗慢性透析而致的中重度UHPT患者的临床疗效良好,安全性较高。     

西那卡塞联合小剂量骨化三醇治疗终末期肾脏病继发性甲状旁腺功能亢进的疗效分析

目的 探讨西那卡塞联合小剂量骨化三醇与骨化三醇冲击疗法对终末期肾脏病继发性甲状旁腺功能亢进(甲旁亢)患者的疗效及安全性.方法 重庆市大足区人民医院2013年1月至2016年5月确诊为终末期肾脏病继发性甲旁亢患者150例,区组随机化分组将患者平均分为3组,每组50例,分别采用西那卡塞治疗、骨化三醇冲击治疗、西那卡塞联合小剂量骨化三醇治疗.其中,西那卡塞联合小剂量骨化三醇组采用盐酸西那卡塞片口服,初始25 mg·d-1,整片吞服;随后每2~4周根据患者耐受情况调整1次剂量,最大剂量75 mg·d-1;同时,口服骨化三醇胶丸,初始0.25μg·d-1,每2~4周调整1次剂量,最大剂量0.5μg·d-1.检测三组患者治疗前及治疗后6个月血钙、血磷含量水平,并对全段甲状旁腺激素(iPTH)进行检测.结果 骨化三醇冲击治疗组治疗后6个月血钙、血磷与治疗前比较明显升高[血钙(2.12±0.62)mmol·L-1比(2.47±0.59)mmol·L-1,t=2.827,P=0.007;血磷[(1.72±0.42)mmol·L-1比(1.95±0.56)mmol·L-1,t=2.366,P=0.022],而iPTH明显下降[iPTH 560.58(334.2~728.47)pg·mL-1比331.23(213.95~424.62)pg·mL-1,Z=4.387,P<0.001];西那卡塞治疗组与西那卡塞联合小剂量骨化三醇治疗组血清磷水平、iPTH与治疗前比较明显下降(P<0.05)[血磷西那卡塞治疗组(1.46±0.72)mmol·L-1比(1.73±0.58)mmol·L-1,t=2.034,P=0.047,血磷西那卡塞联合小剂量骨化三醇治疗组(1.44±0.63)mmol·L-1比(1.76±0.39)mmol·L-1,t=3.014,P=0.004,iPTH西那卡塞治疗组277.02(180.34~344.56)pg·mL-1比544.11(386.8~749.42)pg·mL-1,Z=5.237,P<0.001,iPTH西那卡塞联合小剂量骨化三醇治疗组194.85(132.04~295.64)pg·mL-1比575.49(438.04~665.65)pg·mL-1,Z=6.144,P<0.001],且西那卡塞联合小剂量骨化三醇治疗组血钙水平未见明显影响(P>0.05),而单纯西那卡塞治疗组的血钙水平较治疗前明显下降(P<0.05).结论 西那卡塞联合小剂量骨化三醇治疗终末期肾病继发性甲旁亢患者可降低血磷水平,还可以降低iPTH,但不影响血钙,不容易出现低钙血症,降低骨饥饿综合征的发生.     

西那卡塞对终末期肾病患者继发性甲状旁腺功能亢进影响的 Meta 分析

摘要： 目的 评价西那卡塞治疗终末期肾病患者继发性甲状旁腺功能亢进的有效性和安全性。方法 纳入拟钙剂治疗终末期肾病患者继发性甲状旁腺功能亢进的随机对照研究。计算机检索 MEDLINE（1966.1—2014.9）、 OVID（1963.1—2014.9）、 中文万方数据库（1996.1—2014.9）、 CNKI（1979.1—2014.9）、 Cochrane 图书馆临床对照试验资料库。手工检索已发表或未发表的相关文献, 包括会议摘要等。由 2 名评价员独立对纳入的文献进行质量评价和数据提取, 用 RevMan5.2 软件进行 Meta 分析。结果 共纳入 19 项随机对照试验, 共 7 702 例患者。Meta 分析结果显示, 西那卡塞与传统治疗方法相比, 可以显著降低甲状旁腺素 （WMD=-301.54 µg/L, 95%CI： -344.38～-258.7 µg/L, P＜0.05）, 降低血钙 （WMD=-8.3 mg/L, 95%CI： -9.1～-7.4 mg/L, P＜0.05）, 降低血磷 （WMD=-3.4 mg/L, 95%CI： -4.6～ -2.3 mg/L, P＜0.05）。两组总体不良反应发生率相近 （RR=1.03, 95%CI： 0.98～1.09, P＞0.05）。西那卡塞组主要不良反应包括恶心（RR=2.05, 95%CI： 1.53～2.75, P＜0.05）, 呕吐（RR=2.00, 95%CI： 1.78～2.23, P＜0.05）, 腹泻（RR=1.15, 95%CI： 1.03～1.30, P＜0.05）, 以及无症状的低钙血症 （RR=7.60, 95%CI： 5.61～10.30, P＜0.05）, 但均为短暂且不严重的不良反应。2 组病死率相近（RR =0.97, 95%CI： 0.89～1.05, P＞0.05）。结论 西那卡塞抑制透析患者继发性甲状旁腺功能亢进, 降低血钙和血磷, 不增加病死率, 但增加恶心、 呕吐、 腹泻和低钙血症的风险。