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Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism
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)...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760337/ https://www.ncbi.nlm.nih.gov/pubmed/31369089 http://dx.doi.org/10.1210/jc.2019-01010 |
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author | Mannstadt, Michael Clarke, Bart L Bilezikian, John P Bone, Henry Denham, Douglas Levine, Michael A Peacock, Munro Rothman, Jeffrey Shoback, Dolores M Warren, Mark L Watts, Nelson B Lee, Hak-Myung Sherry, Nicole Vokes, Tamara J |
author_facet | Mannstadt, Michael Clarke, Bart L Bilezikian, John P Bone, Henry Denham, Douglas Levine, Michael A Peacock, Munro Rothman, Jeffrey Shoback, Dolores M Warren, Mark L Watts, Nelson B Lee, Hak-Myung Sherry, Nicole Vokes, Tamara J |
author_sort | Mannstadt, Michael |
collection | PubMed |
description | 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 mg(2)/dL(2), 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. |
format | Online Article Text |
id | pubmed-6760337 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-67603372019-10-02 Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism Mannstadt, Michael Clarke, Bart L Bilezikian, John P Bone, Henry Denham, Douglas Levine, Michael A Peacock, Munro Rothman, Jeffrey Shoback, Dolores M Warren, Mark L Watts, Nelson B Lee, Hak-Myung Sherry, Nicole Vokes, Tamara J J Clin Endocrinol Metab Clinical Research Articles 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 mg(2)/dL(2), 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. Endocrine Society 2019-08-01 /pmc/articles/PMC6760337/ /pubmed/31369089 http://dx.doi.org/10.1210/jc.2019-01010 Text en Copyright © 2019 Endocrine Society https://creativecommons.org/licenses/by/4.0/ This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Clinical Research Articles Mannstadt, Michael Clarke, Bart L Bilezikian, John P Bone, Henry Denham, Douglas Levine, Michael A Peacock, Munro Rothman, Jeffrey Shoback, Dolores M Warren, Mark L Watts, Nelson B Lee, Hak-Myung Sherry, Nicole Vokes, Tamara J Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism |
title | Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism |
title_full | Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism |
title_fullStr | Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism |
title_full_unstemmed | Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism |
title_short | Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism |
title_sort | safety and efficacy of 5 years of treatment with recombinant human parathyroid hormone in adults with hypoparathyroidism |
topic | Clinical Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760337/ https://www.ncbi.nlm.nih.gov/pubmed/31369089 http://dx.doi.org/10.1210/jc.2019-01010 |
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