Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial

被引：9

作者：

Sun, Chengjun ^{[1
]}

Lu, Biao ^{[2
]}

Liu, Yu ^{[3
]}

Zhang, Yaqin ^{[4
]}

Wei, Haiyan ^{[5
]}

Hu, Xu ^{[6
]}

Hu, Pei ^{[7
]}

Zhao, Qian ^{[7
]}

Liu, Yanling ^{[8
]}

Ye, Kan ^{[9
]}

Wang, Kan ^{[10
]}

Gu, Zaiyan ^{[11
]}

Liu, Zheng ^{[12
]}

Ye, Jin ^{[13
]}

Zhang, Hongxiao ^{[14
]}

Zhu, Hong ^{[15
]}

Jiang, Zhihong ^{[16
]}

Liu, Yanjie ^{[17
]}

Wan, Naijun ^{[18
]}

Yan, Chengming ^{[19
]}

Yin, Jianying ^{[20
]}

Ying, Lirong ^{[21
]}

Huang, Feng ^{[22
]}

Yin, Qingjin ^{[23
]}

Xi, Li ^{[1
]}

Luo, Feihong ^{[1
]}

Cheng, Ruoqian ^{[1
]}

机构：

[1] Fudan Univ, Childrens Hosp, Dept Pediat Endocrinol & Inherited Metab Dis, Shanghai, Peoples R China

[2] Ningxia Med Univ, Gen Hosp, Dept Pediat, Yinchuan, Ningxia, Peoples R China

[3] Maternal & Child Hlth Care Hosp Guiyang, Dept Endocrine & Genet Metab, Guiyang, Peoples R China

[4] Maternal & Child Hlth Care Hosp Hainan Prov, Dept Child Hlth, Haikou, Hainan, Peoples R China

[5] Zhengzhou Univ, Henan Prov Hosp, Dept Pediat Endocrinol & Inherited Metab Dis, Zhengzhou, Peoples R China

[6] Luan Peoples Hosp, Dept Pediat, Luan, Peoples R China

[7] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Complex Severe & Rare Dis,Beijing K, Peking Union Med Coll Hosp,Natl Med Prod Adm NMPA, Key Lab Clin Res & Evaluat Drug,Clin Pharmacol Re, Beijing, Peoples R China

[8] Nanchang Univ, Affiliated Hosp 2, Dept Pediat, Nanchang, Jiangxi, Peoples R China

[9] Nanjing Med Univ, Affiliated Suzhou Hosp, Dept Child Hlth, Suzhou, Peoples R China

[10] Zhejiang Univ, Sch Med, Jinhua Hosp, Dept Pediat, Jinhua, Zhejiang, Peoples R China

[11] Jiaxing First Hosp, Dept Pediat, Jiaxing, Peoples R China

[12] Taian Maternal & Child Hlth Care Hosp, Dept Pediat, Tai An, Shandong, Peoples R China

[13] Jiangsu Prov Hosp Chinese Med, Dept Pediat, Nanjing, Peoples R China

[14] Lanzhou Univ, Hosp 2, Dept Pediat, Lanzhou, Peoples R China

[15] First Peoples Hosp Changzhou, Dept Pediat, Changzhou, Jiangsu, Peoples R China

[16] Henan Univ Sci & Technol, Affiliated Hosp 1, Dept Pediat, Luoyang, Peoples R China

[17] Inner Mongolia Peoples Hosp, Dept Pediat, Hohhot, Peoples R China

[18] Jishuitan Hosp, Dept Pediat, Beijing, Peoples R China

[19] Anhui Med Univ, Maternal & Child Hlth Clin Coll, Anhui Prov Matern & Child Hlth Hosp, Dept Pediat, Hefei, Peoples R China

[20] Hebei Gen Hosp, Dept Pediat, Shijiazhuang, Hebei, Peoples R China

[21] Cixi Peoples Hosp, Dept Pediat, Cixi, Peoples R China

[22] Nantong Univ, Affiliated Hosp, Dept Pediat, Nantong, Peoples R China

[23] Chengdu Childrens Specialized Hosp, Dept Internal Med, Chengdu, Peoples R China

来源：

FRONTIERS IN ENDOCRINOLOGY | 2021年 / 12卷

关键词：

growth hormone deficiency; PEGylated recombinant human growth hormone; PEG-rhGH; IGF-2; children; PREPUBERTAL CHILDREN; GH PREPARATION; EFFICACY; LB03002;

D O I：

10.3389/fendo.2021.779365

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ContextLong-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending. ObjectiveWe studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children. Design, Setting, and PatientsThis multicenter, phase IV trial with a non-inferiority threshold >= 20% enrolled 585 Tanner stage I GHD children. InterventionSubjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks. Main Outcome MeasureThe primary outcome was height SD scores for chronological age (HtSDS(CA)) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes. ResultsAt week 26, the median HtSDS(CA) changed from -2.75, -2.82, and -2.78 to -2.31, -2.43, and -2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDS(CA) was 0.17 +/- 0.28 between weekly and biweekly PEG-rhGH, and 0.17 +/- 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%-90.34% and 76.08%-90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups. ConclusionsAlthough notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions.

引用

页数：11

共 22 条

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