Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty

A final report of a phase 3 multicenter trial

Lawrence Silverman, E. Kirk Neely, Gad B. Kletter, Katherine Lewis, Surya Chitra, Oksana Terleckyj, Erica A. Eugster

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Context and Objective: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. Design: This was a phase 3, prospective, open-label study. Setting and Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase. Outcome Measures: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. Results: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy. Conclusions: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP.

Original languageEnglish (US)
Pages (from-to)2354-2363
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Multicenter Studies
Gonadotropin-Releasing Hormone
Labels
Patient treatment
Therapeutics
Gonadotropins
Bone
Hormones
Recovery
histrelin
Central Precocious Puberty
Outcome Assessment (Health Care)
Bone and Bones
Growth

All Science Journal Classification (ASJC) codes

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

Cite this

@article{33044c0fd8f14c60a5f62d10a7ff993c,
title = "Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty: A final report of a phase 3 multicenter trial",
abstract = "Context and Objective: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. Design: This was a phase 3, prospective, open-label study. Setting and Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase. Outcome Measures: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. Results: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy. Conclusions: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP.",
author = "Lawrence Silverman and Neely, {E. Kirk} and Kletter, {Gad B.} and Katherine Lewis and Surya Chitra and Oksana Terleckyj and Eugster, {Erica A.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1210/jc.2014-3031",
language = "English (US)",
volume = "100",
pages = "2354--2363",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "6",

}

Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty : A final report of a phase 3 multicenter trial. / Silverman, Lawrence; Neely, E. Kirk; Kletter, Gad B.; Lewis, Katherine; Chitra, Surya; Terleckyj, Oksana; Eugster, Erica A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 6, 01.06.2015, p. 2354-2363.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty

T2 - A final report of a phase 3 multicenter trial

AU - Silverman, Lawrence

AU - Neely, E. Kirk

AU - Kletter, Gad B.

AU - Lewis, Katherine

AU - Chitra, Surya

AU - Terleckyj, Oksana

AU - Eugster, Erica A.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Context and Objective: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. Design: This was a phase 3, prospective, open-label study. Setting and Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase. Outcome Measures: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. Results: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy. Conclusions: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP.

AB - Context and Objective: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. Design: This was a phase 3, prospective, open-label study. Setting and Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase. Outcome Measures: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. Results: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy. Conclusions: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP.

UR - http://www.scopus.com/inward/record.url?scp=84930813914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930813914&partnerID=8YFLogxK

U2 - 10.1210/jc.2014-3031

DO - 10.1210/jc.2014-3031

M3 - Article

VL - 100

SP - 2354

EP - 2363

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -