Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism.
Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism.
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DOI：
10.1210/jendso/bvad043
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发表时间：
2023-03-06
影响因子：
4.1
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慢性甲状旁腺功能减退症通常用口服钙和活性维生素D治疗，以达到并维持目标血清钙和磷水平，但有些患者仍然控制不佳。评价重组人甲状旁腺激素（1-84）（rhPTH（1 - 84））治疗的长期安全性和有效性。这是一项在12家美国临床试验机构开展的开放标签扩展研究。纳入慢性甲状旁腺功能减退的成人（n = 49）。治疗组给予rhPTH（1-84）治疗6年。主要结果指标为安全性、生化指标、口服补充剂量、骨指数。38例患者（77.6%）完成了研究。在整个72个月内，平均白蛋白校正血清钙在2.00 - 2.25 mmol/L（8.0-9.0 mg/dL）范围内。 在基线时，65%有测量值的患者（n = 24/37）为高尿钙;其中，54%（n = 13/24）在第72个月时尿钙正常。平均血清磷从基线时的1.6 ± 0.19 mmol/L（n = 49）降至第72个月时的1.3 ± 0.20 mmol/L（n = 36）。 平均估计肾小球滤过率稳定。51.0%的患者（n = 25/49）报告了rhPTH（1-84）相关不良事件;除1起事件外，所有事件的严重程度均为轻度/中度。平均口服钙补充减少45% ± 113.6%，骨化三醇减少74% ± 39.3%。骨转换标志物在第32个月下降至高于治疗前值的平台期;仅1型胶原的氨基末端前肽仍在参考范围之外。平均骨矿物质密度z评分在三分之一半径处下降，在其他部位稳定。6年的rhPTH（1-84）治疗与生化参数的持续改善、高钙尿症患者百分比的降低、肾功能稳定和补充剂需求减少相关。rhPTH（1-84）耐受性良好;未发现新的安全性信号。
Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled. To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment. This was an open-label extension study at 12 US centers. Adults (n = 49) with chronic hypoparathyroidism were included. The intervention was rhPTH(1-84) for 6 years. The main outcome measures were safety, biochemical measures, oral supplement doses, bone indices. Thirty-eight patients (77.6%) completed the study. Throughout 72 months, mean albumin-adjusted serum calcium was within 2.00 to 2.25 mmol/L (8.0-9.0 mg/dL). At baseline, 65% of patients with measurements (n = 24/37) were hypercalciuric; of these, 54% (n = 13/24) were normocalciuric at month 72. Mean serum phosphorus declined from 1.6 ± 0.19 mmol/L at baseline (n = 49) to 1.3 ± 0.20 mmol/L at month 72 (n = 36). Mean estimated glomerular filtration rate was stable. rhPTH(1-84)-related adverse events were reported in 51.0% of patients (n = 25/49); all but 1 event were mild/moderate in severity. Mean oral calcium supplementation reduced by 45% ± 113.6% and calcitriol by 74% ± 39.3%. Bone turnover markers declined by month 32 to a plateau above pretreatment values; only aminoterminal propeptide of type 1 collagen remained outside the reference range. Mean bone mineral density z score fell at one-third radius and was stable at other sites. 6 years of rhPTH(1-84) treatment was associated with sustained improvements in biochemical parameters, a reduction in the percentage of patients with hypercalciuria, stable renal function, and decreased supplement requirements. rhPTH(1-84) was well tolerated; no new safety signals were identified.