Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota.
J Clin Endocrinol Metab. 2019 Nov 1;104(11):5136-5147. doi: 10.1210/jc.2019-01010.
Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency.
To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)].
Open-label extension study; 5-year interim analysis.
12 US centers.
Adults (N = 49) with chronic hypoparathyroidism.
INTERVENTION(S): rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum.
MAIN OUTCOME MEASURE(S): Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal.
Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline.
Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.
常规的甲状旁腺功能减退症的治疗方法是口服钙剂和活性维生素 D，其目的是纠正低钙血症，但不能解决甲状旁腺激素缺乏引起的其他生理缺陷。
评估重组人甲状旁腺激素（1-84）[rhPTH（1-84）]的长期安全性和耐受性。
开放标签扩展研究；5 年中期分析。
美国 12 个中心。
患有慢性甲状旁腺功能减退症的成年人（N=49）。
rhPTH（1-84）初始剂量为 25 或 50μg/d，允许将 25μg 调整至最高 100μg/d。
安全性参数；复合疗效结果是指口服钙剂（或≤500mg/d）和骨化三醇（或≤0.25μg/d）剂量减少≥50%的患者比例，以及与基线相比，白蛋白校正血清钙正常化或维持，不超过正常值上限。
40 名患者完成了 60 个月的治疗。平均白蛋白校正血清钙水平保持在 8.2 至 8.7mg/dL 之间。在基线至 60 个月期间，尿钙、血清磷和钙磷乘积的水平分别降低了 101.2±236.24mg/24 小时、1.0±0.78mg/dL 和 8.5±8.29mg2/dL2。血清肌酐水平和估计肾小球滤过率保持不变。48 名患者（98.0%；低钙血症 36.7%；肌肉痉挛 32.7%；感觉异常 30.6%；鼻窦炎 30.6%；恶心 30.6%）报告了治疗中出现的不良事件（AE），13 名患者（26.5%）出现了严重的 AE。在第 60 个月时，28 名患者（70.0%）达到了复合疗效结果。骨转换标志物增加，在约 12 个月时达到峰值，然后下降至仍高于基线的值。
rhPTH（1-84）治疗 5 年显示出与先前研究一致的安全性，并改善了关键的生化参数。
