TY - JOUR
T1 - Safety and Efficacy of 5 Years of Treatment with Recombinant Human Parathyroid Hormone in Adults with Hypoparathyroidism
AU - Mannstadt, Michael
AU - Clarke, Bart L.
AU - Bilezikian, John P.
AU - Bone, Henry
AU - Denham, Douglas
AU - Levine, Michael A.
AU - Peacock, Munro
AU - Rothman, Jeffrey
AU - Shoback, Dolores M.
AU - Warren, Mark L.
AU - Watts, Nelson B.
AU - Lee, Hak Myung
AU - Sherry, Nicole
AU - Vokes, Tamara J.
N1 - Funding Information:
The clinical trial was funded by Shire Human Genetic Therapies, Inc., Lexington, Massachusetts, a member of the Takeda group of companies. Under the direction of the authors and funded by Shire International GbmH (Zug, Switzerland), a member of the Takeda group of companies, editorial support and writing assistance were provided by Heather Heerssen, PhD, of Complete Healthcare Communications, LLC, a CHC Group company, North Wales, Pennsylvania We thank Alan Krasner and John Caminis (former employees of Shire Human Genetic Therapies, a member of the Takeda group of companies, Lexington, MA) for helpful insights and comments on the manuscript. In addition, we thank Sharon Kunder (employee of Shire Human Genetic Therapies a member of the Takeda group of companies), who was safety scientist. A portion of these data were presented at the 100th Annual Meeting of the Endocrine Society, Chicago, Illinois, 17-20 March 2019.
Publisher Copyright:
Copyright © 2019 Endocrine Society.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Context: 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. Objective: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)]. Design: Open-label extension study; 5-year interim analysis. Setting: 12 US centers. Patients: 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. Results: 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. Conclusion: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.
AB - Context: 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. Objective: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)]. Design: Open-label extension study; 5-year interim analysis. Setting: 12 US centers. Patients: 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. Results: 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. Conclusion: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.
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U2 - 10.1210/jc.2019-01010
DO - 10.1210/jc.2019-01010
M3 - Article
C2 - 31369089
AN - SCOPUS:85072628898
SN - 0021-972X
VL - 104
SP - 5136
EP - 5147
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -