长期聚乙二醇化人生长激素治疗生长激素缺乏症儿童：一项大型、前瞻性、真实世界研究。

Long-term Pegylated GH for Children With GH Deficiency: A Large, Prospective, Real-world Study.

机构信息

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Department of Endocrinology, National Clinical Research Center for Child Health, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.

出版信息

J Clin Endocrinol Metab. 2023 Jul 14;108(8):2078-2086. doi: 10.1210/clinem/dgad039.

CONTEXT

The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited.

OBJECTIVE

This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes.

DESIGN

A prospective, observational, posttrial study (NCT03290235).

SETTING, PARTICIPANTS AND INTERVENTION: Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months.

MAIN OUTCOMES MEASURES

Height SD score (Ht SDS) at 12, 24, and 36 months.

RESULTS

A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred.

CONCLUSIONS

PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.

背景

聚乙二醇重组人生长激素（PEG-rhGH）治疗儿童生长激素缺乏症（GHD）的长期证据有限。

目的

本研究旨在评估真实世界中聚乙二醇 rhGH 治疗儿童 GHD 的有效性和安全性，并研究剂量对患者结局的影响。

设计

前瞻性、观察性、试验后研究（NCT03290235）。

地点、参与者和干预措施：81 家中国中心的 GHD 患儿参加了 4 项单独的临床试验，接受每周 0.2mg/kg/wk（高剂量）或 0.1 至 <0.2mg/kg/wk（低剂量）PEG-rhGH 治疗 30 个月。

主要结局测量指标

12、24 和 36 个月时身高标准差评分（Ht SDS）。

结果

共有 1170 名患儿参加了本试验后研究，高剂量亚组 642 例，低剂量亚组 528 例。总体人群治疗后 Ht SDS 显著改善（P<0.0001），平均变化分别为 0.53±0.30、0.89±0.48、1.35±0.63、1.63±0.75 个月、6 个月、12 个月、24 个月和 36 个月。此外，治疗后 6、12、24 和 36 个月，高剂量亚组 Ht SDS 的改善较低剂量亚组显著（均 P<0.05）。共发生 12 例（1.03%）严重不良事件。无与治疗相关的严重不良事件，无因不良事件导致停药或死亡的情况发生。