PMID- 31369089
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 104
IP  - 11
DP  - 2019 Nov 1
TI  - Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid 
      Hormone in Adults With Hypoparathyroidism.
PG  - 5136-5147
LID - 10.1210/jc.2019-01010 [doi]
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 microg/d initially, with 25-microg adjustments permitted to a 100 
      microg/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 microg/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  approximately 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.
CI  - Copyright (c) 2019 Endocrine Society.
FAU - Mannstadt, Michael
AU  - Mannstadt M
AD  - Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, 
      Boston, Massachusetts.
FAU - Clarke, Bart L
AU  - Clarke BL
AD  - Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, 
      Rochester, Minnesota.
FAU - Bilezikian, John P
AU  - Bilezikian JP
AD  - Division of Endocrinology, College of Physicians and Surgeons, Columbia 
      University, New York, New York.
FAU - Bone, Henry
AU  - Bone H
AD  - Michigan Bone and Mineral Clinic, PC, Detroit, Michigan.
FAU - Denham, Douglas
AU  - Denham D
AD  - Clinical Trials of Texas, Inc., San Antonio, Texas.
FAU - Levine, Michael A
AU  - Levine MA
AD  - Division of Endocrinology and Diabetes and Center for Bone Health, Children's 
      Hospital of Philadelphia, Philadelphia, Pennsylvania.
FAU - Peacock, Munro
AU  - Peacock M
AD  - Department of Medicine, Division of Endocrinology, Indiana University School of 
      Medicine, Indianapolis, Indiana.
FAU - Rothman, Jeffrey
AU  - Rothman J
AD  - University Physicians Group - Research Division, Staten Island, New York.
FAU - Shoback, Dolores M
AU  - Shoback DM
AD  - Endocrine Research Unit, Department of Medicine, San Francisco Veterans Affairs 
      Medical Center, University of California, San Francisco, California.
FAU - Warren, Mark L
AU  - Warren ML
AD  - Endocrinology and Metabolism, Physicians East, Greenville, North Carolina.
FAU - Watts, Nelson B
AU  - Watts NB
AD  - Osteoporosis and Bone Health Services, Mercy Health, Cincinnati, Ohio.
FAU - Lee, Hak-Myung
AU  - Lee HM
AD  - Shire Human Genetic Therapies, Inc., a member of the Takeda group of companies, 
      Lexington, Massachusetts.
FAU - Sherry, Nicole
AU  - Sherry N
AD  - Shire Human Genetic Therapies, Inc., a member of the Takeda group of companies, 
      Cambridge, Massachusetts.
FAU - Vokes, Tamara J
AU  - Vokes TJ
AD  - Section of Endocrinology, University of Chicago Medicine, Chicago, Illinois.
LA  - eng
SI  - ClinicalTrials.gov/NCT01297309
GR  - I01 CX001514/CX/CSRD VA/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Calcium, Dietary)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Recombinant Proteins)
RN  - FXC9231JVH (Calcitriol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Calcitriol/therapeutic use
MH  - Calcium/blood/therapeutic use
MH  - Calcium, Dietary/therapeutic use
MH  - Female
MH  - Hormone Replacement Therapy/*adverse effects/*methods
MH  - Humans
MH  - Hypoparathyroidism/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Parathyroid Hormone/*adverse effects/*therapeutic use
MH  - Recombinant Proteins
MH  - Treatment Outcome
PMC - PMC6760337
COIS- Disclosure Summary: The authors have served in the following capacities for 
      Shire, a member of the Takeda group of companies. M.M. and M.A.L. have served as 
      advisory board members, consultants, and research investigators. B.L.C., J.P.B, 
      and D.M.S. have served as advisory board members, consultants, grant recipients, 
      and research investigators. H.B. and N.B.W. have served as research investigators 
      and speakers. D.D. is a grant recipient. M.P. has served as a grant recipient and 
      research investigator. J.R. has served as an advisory board member, research 
      investigator, and speaker. T.J.V. has served as an advisory board member and 
      consultant. M.L.W. has served as a grant recipient, research investigator, and 
      speaker. H.-M.L. and N.S. are employees of Shire Human Genetic Therapies, Inc., a 
      member of the Takeda group of companies, and declare ownership interest in 
      Takeda. The datasets, including redacted study protocol, redacted statistical 
      analysis plan, and individual participant's data behind the results reported in 
      this article, will be available three months after the submission of a request to 
      researchers who provide a methodologically sound proposal after 
      de-identification, in compliance with applicable privacy laws, data protection, 
      and requirements for consent and anonymization. Data requests should follow the 
      process outlined in the Data Sharing section on Shire's website 
      (www.shiretrials.com) and should be directed to clinicaltrialdata@shire.com. For 
      approved requests, the researchers will be provided access to 
      de-identified/anonymized data on a password-protected website upon Shire's 
      receipt of a signed Data Sharing Agreement.
EDAT- 2019/08/02 06:00
MHDA- 2020/06/02 06:00
PMCR- 2019/08/01
CRDT- 2019/08/02 06:00
PHST- 2019/04/30 00:00 [received]
PHST- 2019/07/26 00:00 [accepted]
PHST- 2019/08/02 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2019/08/02 06:00 [entrez]
PHST- 2019/08/01 00:00 [pmc-release]
AID - 5540965 [pii]
AID - 201901010 [pii]
AID - 10.1210/jc.2019-01010 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2019 Nov 1;104(11):5136-5147. doi: 
      10.1210/jc.2019-01010.