36-Month Treatment Experience of Two Doses of Leuprolide Acetate 3-Month Depot for Children With Central Precocious Puberty
36-Month Treatment Experience of Two Doses of Leuprolide Acetate 3-Month Depot for Children With Central Precocious Puberty
复制标题
DOI：
10.1210/jc.2013-4471
复制
发表时间：
2014-09-01
影响因子：
5.8
通讯作者：
Bacher, Peter
中科院分区：
文献类型：
--
作者：
Lee, Peter A.;Klein, Karen;Bacher, Peter
背景：我们最近证实了醋酸亮丙瑞林3个月库11.25和30 mg治疗中枢性早熟(CPP)的短期(6个月)疗效和安全性。目的：评估长期(36个月)下丘脑-垂体-性腺轴抑制和醋酸亮丙瑞林3个月库11.25和30 mg对中枢性早熟儿童的安全性。设计：开放标签，延长36个月。设置：20个儿科内分泌中心。患者：72名儿童(平均年龄8.5+/1.6岁；干预：肌注醋酸亮丙瑞林(11.25或30 mg)每3个月给药一次。主要观察指标：促黄体生成素峰值、雌二醇、睾酮、生长速度、青春期进展和不良事件。结果：11.25 mg组34名受试者中29名和30 mg组38名受试者中36名在第1天后所有时间点的黄体生成素水平均为4mIU/ml。所有七名在任何时候逃脱了促黄体生成素抑制的受试者仍然将性类固醇浓度维持在青春期前的水平，并且没有表现出青春期进展的迹象。注射部位疼痛是最常见的(总体26.4%)，两组间的疗效相当。无不良反应导致研究药物停用。36个月以上的安全性与6个月核心研究期间观察到的安全性相似。结论：两种剂量的醋酸亮丙瑞林3个月库具有可接受的安全性，并在研究36个月期间或青春期准备好之前维持对大多数CPP儿童的促黄体生成素抑制。
Context: We have recently demonstrated short-term (6-month) efficacy and safety of leuprolide acetate 3-month depot 11.25 and 30 mg in children with central precocious puberty (CPP).Objective: To assess long-term (36-month) hypothalamic-pituitary-gonadal axis suppression and safety of leuprolide acetate 3-month depot 11.25 and 30 mg in children with CPP.Design: Open-label, 36-month extension.Setting: Twenty pediatric endocrine centers.Patients: Seventy-two children (mean age, 8.5 +/- 1.6 y; 65 females) with CPP completed and showed maintenance of LH suppression after a 6-month lead-in study.Intervention: Leuprolide acetate depot (11.25 or 30 mg) administered im every 3 months.Main Outcome Measures: Peak-stimulated LH, estradiol, T, growth rate, pubertal progression, and adverse events (AEs).Results: Twenty-nine of 34 subjects in the 11.25-mg group and 36 of 38 subjects in the 30-mg group had LH values < 4 mIU/mL after day 1 at all time points. All seven subjects who escaped LH suppression at any time still maintained sex steroid concentrations at prepubertal levels and showed no signs of pubertal progression. AEs were comparable between groups, with injection site pain being the most common (26.4% overall). No AE led to discontinuation of study drug. The safety profile over 36 months was comparable to that observed during the 6-month pivotal study.Conclusions: The two doses of leuprolide acetate 3-month depot were associated with an acceptable safety profile and provided maintenance of LH suppression in the majority of children with CPP during the 36 months of the study or until readiness for puberty.