Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

Michael Mannstadt, Bart L. Clarke, John P. Bilezikian, Henry Bone, Douglas Denham, Michael A. Levine, Munro Peacock, Jeffrey Rothman, Dolores M. Shoback, Mark L. Warren, Nelson B. Watts, Hak Myung Lee, Nicole Sherry, Tamara J. Vokes

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5136-5147
Number of pages12
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number11
DOIs
StatePublished - Nov 1 2019

Fingerprint

Hypoparathyroidism
Calcium
Safety
Parathyroid Hormone
Hypocalcemia
Serum Albumin
Phosphorus
Albumins
Therapeutics
Paresthesia
Calcitriol
Bone Remodeling
Sinusitis
Composite materials
Spasm
Serum
Glomerular Filtration Rate
Vitamin D
Nausea
Muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

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.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 11, 01.11.2019, p. 5136-5147.

Research output: Contribution to journalArticle

Mannstadt, M, Clarke, BL, Bilezikian, JP, Bone, H, Denham, D, Levine, MA, Peacock, M, Rothman, J, Shoback, DM, Warren, ML, Watts, NB, Lee, HM, Sherry, N & Vokes, TJ 2019, 'Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism', The Journal of clinical endocrinology and metabolism, vol. 104, no. 11, pp. 5136-5147. https://doi.org/10.1210/jc.2019-01010
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. In: The Journal of clinical endocrinology and metabolism. 2019 ; Vol. 104, No. 11. pp. 5136-5147.
@article{c9f6a416e0f74180aafee22c342279e3,
title = "Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism",
abstract = "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.",
author = "Michael Mannstadt and Clarke, {Bart L.} and Bilezikian, {John P.} and Henry Bone and Douglas Denham and Levine, {Michael A.} and Munro Peacock and Jeffrey Rothman and Shoback, {Dolores M.} and Warren, {Mark L.} and Watts, {Nelson B.} and Lee, {Hak Myung} and Nicole Sherry and Vokes, {Tamara J.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1210/jc.2019-01010",
language = "English (US)",
volume = "104",
pages = "5136--5147",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "11",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85072628898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072628898&partnerID=8YFLogxK

U2 - 10.1210/jc.2019-01010

DO - 10.1210/jc.2019-01010

M3 - Article

C2 - 31369089

AN - SCOPUS:85072628898

VL - 104

SP - 5136

EP - 5147

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -