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

Author:

Hou Ling1,Huang Ke2ORCID,Gong Chunxiu3,Luo Feihong4,Wei Haiyan5,Liang Liyang6,Du Hongwei7,Zhang Jianping8,Zhong Yan9,Chen Ruimin10,Chen Xinran11,Pan Jiayan12,Jin Xianjiang13,Zeng Ting14,Liao Wei15,Liu Deyun16,Lan Dan17,Zhu Shunye18,Dong Zhiya19,Ma Huamei20,Yang Yu21,Xiong Feng22,Lu Ping23,Cheng Shengquan24,Gu Xuefan25,Jin Runming26,Liu Yu27,Wu Jinzhun28,Xu Xu29,Chen Linqi30,Dong Qin31,Pan Hui32,Su Zhe33,Liu Lijun34,Luo Xiaoming35,Ni Shining36,Chen Zhihong37,Hu Yuhua38,Wang Chunlin39,Liu Jing40,Liu Li41,Lu Biao42,Wang Xinli43,Wang Yunfeng44,Yang Fan45,Zhang Manyan46,Cao Lizhi47,Liu GeLi48,Yao Hui49,Zhan Yaqin50,Dai Mingjuan51,Li Guimei52,Li Li53,Liu Yanjie54,Wang Kan55,Xiao Yanfeng56,Zhang Xingxing57,Dong Junhua58,Gu Zaiyan59,Ying Lirong60,Huang Feng61,Liu Yanling62,Liu Zheng63,Ye Jin64,Zhao Dongmei65,Hu Xu66,Jiang Zhihong67,Ye Kan68,Zhu Hong69,Chen Shaoke70,Chen Xiaobo71,Wan Naijun72,Xu Zhuangjian73,Yin Qingjin74,Zhang Hongxiao75,Huang Xiaodong76,Yin Jianying77,Zhang Huifeng78,Li Pin79,Yin Ping80,Fu Junfen2ORCID,Luo XiaoPing1ORCID

Affiliation:

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

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

3. Department of Endocrine and Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Centre for Children's Health , Beijing 100045 , China

4. Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University , Shanghai 201102 , China

5. Department of Endocrinology and Metabolism, Genetics, Henan Children's Hospital (Children's Hospital Affiliated to Zhengzhou University) , Zhengzhou 450018 , China

6. Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou 510120 , China

7. Department of Paediatrics, First Hospital of Jilin University , Changchun 130021 , China

8. Department of Pediatrics, Ningbo Women & Children's Hospital , Ningbo 315012 , China

9. Department of Child Health Care, Hunan Children's Hospital , Changsha 410007 , China

10. Department of Endocrinology, Genetics and Metabolism, Fuzhou Children's Hospital of Fujian Medical University , Fuzhou 350005 , China

11. Department of Pediatric Endocrine Genetics and Metabolism, Chengdu Women's and Children's Center Hospital , Chengdu 610074 , China

12. Department of Pediatrics, Wuhu First People's Hospital , Wuhu 241000 , China

13. Department of Genetics and Endocrinology, The Second Affiliated Hospital &Yuying Children's Hospital of Wenzhou Medical University , Wenzhou 325000 , China

14. Department of Child Health Care, Liuzhou Maternilty and Child Heulthcare Hospital , Liuzhou, Guangxi 545001 , China

15. Department of Pediatrics, First Affiliated Hospital of Army Medical University (Thrid Military Medical University) , Chongqing 400038 , China

16. Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University , Hefei 230601 , China

17. Department of Pediatrics, the First Affiliated Hospital of Guangxi Medical University , Nanning 530021 , China

18. Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou 510630 , China

19. Department of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine , Shanghai 200025 , China

20. Department of Pediatrics, The First Affiliated Hospital of Sun Yat-Sen University , Guangzhou 510080 , China

21. Department of Endocrinology and Genetics, Jiangxi Provincial Children's Hospital, Affiliated Children's Hospital of Nanchang University , Nanchang 330006 , China

22. Department of Endocrinology, Children's Hospital of Chongqing Medical University , Chongqing 400016 , China

23. Department of Pediatrics, The First Affiliated Hospital of Kunming Medical University , Kunming 650032 , China

24. Department of Pediatrics, First Affiliated Hospital of Air Force Medical University , Xi’an 710032 , China

25. Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, School of Medicine, Shanghai Jiao Tong University , Shanghai 200092 , China

26. Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 , China

27. Department of Endocrine and Genetic Metabolism, Maternal and Child Health-Care Hospital in Guiyang , Guiyang 550003 , China

28. Department of Pediatrics, the First Affiliated Hospital of Xiamen University , Xiamen 361003 , China

29. Department of Endocrinology, Wuxi Children's Hospital , Wuxi 214023 , China

30. Depatment of Endocrinology, Children's Hospital of Soochow University , Suzhou 215025 , China

31. Department of Pediatrics, Zhejiang Hospital of Traditional Chinese Medicine , Hangzhou 310000 , China

32. Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College , Beijing 100730 , China

33. Department of Endocrinology, Shenzhen Children's Hospital , Shenzhen 518038 , China

34. Department of Endocrinology, Genetics and Metabolism, Hebei Children's Hospital , Shijiazhuang 050031 , China

35. Department of Pediatrics, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College , Hangzhou 310014 , China

36. Department of Endocrinology, Children's Hospital of Nanjing Medical University , Nanjing 210008 , China

37. Department of Pediatric Endocrinology, Metabolism & Gastroenterology, The Affiliated Hospital of Qingdao University , Qingdao 266003 , China

38. Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University , Nanjing 210029 , China

39. Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou 310003 , China

40. Department of Pediatrics, Changchun Children's Hospital , Changchun, Jilin 130000 , China

41. Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center , Guangzhou 510623 , China

42. Department of Pediatrics, General Hospital of Ningxia Medical University , Yinchuan 750004 , China

43. Department of Pediatric, Peking University Third Hospital , Beijing 100191 , China

44. Department of Pediatrics, China-Japan Friendship Hospital , Beijing 100029 , China

45. Department of Pediatrics, West China Second Hospital, Sichuan University , Chengdu 610041 , China

46. Department of Pediatrics, Shaoxing Second Hospital , Shaoxing 312000 , China

47. Department of Pediatrics, Xiangya Hospital, Central South University , Changsha 410008 , China

48. Department of Pediatrics, Tianjin Medical University General Hospital , Tianjin 300052 , China

49. Department of Endocrinology and Metabolism, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430015 , China

50. Department of Child Health, Maternal and Child Health Care Hospital of Hainan Province , Haikou 570206 , China

51. Department of Pediatrics, Hangzhou First People's Hospital , Hangzhou 310022 , China

52. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University , Jinan 250021 , China

53. Department of Pediatrics, The 1st People's Hospital of Yunnan Province , Kunming 650032 , China

54. Department of Pediatrics, Inner Mongolia People's Hospital , Hohhot Inner Mongolia 010017 , China

55. Department of Pediatrics, Jinhua Hospital, Zhejiang University School of Medicine , Jinhua 321000 , China

56. Department of Pediatrics, The 2nd Affiliated Hospital of Medical College of Xi’an Jiaotong University , Xi’an 710004 , China

57. Department of Pediatrics, the Second Xiangya Hospital, Central South University , Changsha 410011 , China

58. Department of Pediatrics, Qilu Hospital of Shandong University , Jinan 250012 , China

59. Department of Pediatrics, Jiaxing First Hospital , Jiaxing 314000 , China

60. Department of Pediatrics, Cixi People's Hospital , Cixi 315300 , China

61. Department of Pediatrics, Affiliated Hospital of Nantong University , Nantong 226000 , China

62. Department of Pediatrics, the Second Affiliated Hospital of Nanchang University , Nanchang 330006 , China

63. Department of Pediatrics, Tai’an Maternal and Child Health Care Hospital , Tai’an, Shandong 271000 , China

64. Department of Pediatrics, Jiangsu Province Hospital of Chinese Medicine , Nanjing 210029 , China

65. Pediatric Research Institute, Qilu Children's Hospital of Shandong University , Jinan, Shandong 250022 , China

66. Department of Pediatrics, Lu’an People's Hospital , Lu’an 237000 , China

67. Department of Pediatric, The First Affiliated Hospital of He’nan University of Science and Technology , Luoyang 471003 , China

68. Department of Child Health, The Affiliated Suzhou Hospital of Nanjing Medical University , Suzhou 215002 , China

69. Department of Pediatrics, The First People's Hospital of Changzhou , Changzhou 213000 , China

70. Department of Pediatrics, The Second Affiliated Hospital of Guangxi Medical University , Nanning 530005 , China

71. Department of Endocrinology, Children's Hospital, Capital Institute of Pediatrics , Beijing 100020 , China

72. Department of Pediatrics, Jishuitan Hospital , Beijing 100035 , China

73. Department of Pediatrics, Affiliated Hospital of Jiangnan University , Wuxi 214122 , China

74. Ward 1, Department of Internal Medicine, Chengdu Children's Specialized Hospital , Chengdu 610015 , China

75. Department of Pediatric, Second Hospital of Lanzhou University , Lanzhou 730030 , China

76. Department of Endocrinology and Genetics, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine , Shanghai 200127 , China

77. Department of Pediatrics, Hebei General Hospital , Shijiazhuang 050051 , China

78. Department of Pediatrics, the Second Hospital of Hebei Medical University , Shijiazhuang 050000 , China

79. Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University , Shanghai 200333 , China

80. School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430030 , China

Abstract

Abstract 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.

Funder

The National Key Research and Development Program of China is funded by Ministry of Science and Technology of the People's Republic of China

The Special Science and Technology Major Project of Hubei Province is funded by Hubei Provincial Science and Technology Department

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference35 articles.

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