Long-term effectiveness and safety of long-acting growth hormone preparation in children with growth hormone deficiency.

Publisher: Walter de Gruyter Country of Publication: Germany NLM ID: 9508900 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2191-0251 (Electronic) Linking ISSN: 0334018X NLM ISO Abbreviation: J Pediatr Endocrinol Metab Subsets: MEDLINE

Publication: Mar. 2011- : Berlin : Walter de Gruyter
Original Publication: London : Freund Pub. House, [1995-

Human Growth Hormone*/deficiency ; Human Growth Hormone*/administration & dosage ; Human Growth Hormone*/therapeutic use ; Growth Disorders*/drug therapy ; Body Height*/drug effects; Humans ; Male ; Child ; Female ; Follow-Up Studies ; Child, Preschool ; Treatment Outcome ; Prognosis ; Hormone Replacement Therapy/methods ; Dwarfism, Pituitary/drug therapy ; Delayed-Action Preparations

Objectives: To evaluate the long-term effectiveness of weekly vs. daily growth hormone (GH) administration in children with GH deficiency.
Methods: This study, part of the "LG Growth Study", included a total of 996 children with GH deficiency (773 receiving daily GH and 193 receiving weekly GH). Anthropometric data were collected at baseline and every 12 months; clinical and laboratory data were collected at baseline and throughout the study.
Results: At baseline, the weekly GH group was older, shorter in mid-parental height (MPH), and had more pubertal boys compared to the daily GH group (age: 8.46 ± 3.44 vs. 7.46 ± 2.89 years, p<0.001; MPH: -0.88 ± 0.73 SD vs. -1.02 ± 0.84 SD, p=0.044; pubertal boys: 34.0 vs. 16.9 %, p=0.006). Height velocity and change in height SDS during the first 12 months were higher in the daily GH group (height velocity: 9.06 ± 1.72 vs. 8.67 ± 1.98 cm/year, p=0.028; height SDS change: 0.78 ± 0.39 vs. 0.61 ± 0.41, p<0.001). However, height SDS at 24 and 48 months were similar between groups. No significant differences in overall height velocity, annualized treatment continuation rate, and safety profile were observed over 48 months.
Conclusions: Weekly GH therapy appears to be an effective and safe alternative to daily GH treatment in children with GH deficiency over a 4-year period. Further research with larger sample sizes and longer follow-up is needed to confirm these findings and assess the extended safety and effectiveness of LAGH.
(© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Richmond, E, Rogol, AD. Treatment of growth hormone deficiency in children, adolescents and at the transitional age. Best Pract Res Clin Endocrinol Metabol 2016;30:749–55. https://doi.org/10.1016/j.beem.2016.11.005 . (PMID: 10.1016/j.beem.2016.11.005)
Yoon, JY, Cheon, CK, Lee, JH, Kwak, MJ, Kim, HJ, Kim, YJ, et al.. Response to growth hormone according to provocation test results in idiopathic short stature and idiopathic growth hormone deficiency. Ann Pediatr Endocrinol Metab 2022;27:37–43. https://doi.org/10.6065/apem.2142110.055 . (PMID: 10.6065/apem.2142110.055)
Lee, HS. The effects of growth hormone treatment on height in short children. Ann Pediatr Endocrinol Metab 2022;27:1–2. https://doi.org/10.6065/apem.2221055edi01 . (PMID: 10.6065/apem.2221055edi01)
Geffner, ME, Ranke, MB, Wajnrajch, MP. An overview of growth hormone therapy in pediatric cases documented in the kabi international growth study (pfizer international growth database). Ann Pediatr Endocrinol Metab 2024;29:3–11. https://doi.org/10.6065/apem.2346206.103 . (PMID: 10.6065/apem.2346206.103)
Allen, DB, Backeljauw, P, Bidlingmaier, M, Biller, BM, Boguszewski, M, Burman, P, et al.. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur J Endocrinol 2016;174:P1–9. https://doi.org/10.1530/eje-15-0873 . (PMID: 10.1530/eje-15-0873)
Grimberg, A, DiVall, SA, Polychronakos, C, Allen, DB, Cohen, LE, Quintos, JB, et al.. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr 2016;86:361–97. https://doi.org/10.1159/000452150 . (PMID: 10.1159/000452150)
Collett-Solberg, PF, Ambler, G, Backeljauw, PF, Bidlingmaier, M, Biller, BMK, Boguszewski, M, et al.. Diagnosis, genetics, and therapy of short stature in children: a growth hormone research society international perspective. Hormone Res Paediatr 2019;92:1–14. https://doi.org/10.1159/000502231 . (PMID: 10.1159/000502231)
Oh, JS, Sohn, B, Choi, Y, Song, K, Suh, J, Kwon, A, et al.. The influence of pituitary volume on the growth response in growth hormone-treated children with growth hormone deficiency or idiopathic short stature. Ann Pediatr Endocrinol Metab 2024;29:95–101. https://doi.org/10.6065/apem.2346052.026 . (PMID: 10.6065/apem.2346052.026)
Burns, EC, Tanner, JM, Preece, MA, Cameron, N. Final height and pubertal development in 55 children with idiopathic growth hormone deficiency, treated for between 2 and 15 years with human growth hormone. Eur J Pediatr 1981;137:155–64. https://doi.org/10.1007/bf00441309 . (PMID: 10.1007/bf00441309)
Kastrup, KW, Christiansen, JS, Andersen, JK, Orskov, H. Increased growth rate following transfer to daily SC administration from three weekly IM injections of HGH in growth hormone deficient children. Acta Endocrinol 1983;104:148–52. https://doi.org/10.1530/acta.0.1040148 . (PMID: 10.1530/acta.0.1040148)
Holdaway, IM, Hunt, P, Manning, P, Cutfield, W, Gamble, G, Ninow, N, et al.. Three-year experience with access to nationally funded growth hormone (GH) replacement for GH-deficient adults. Clin Endocrinol 2015;83:85–90. https://doi.org/10.1111/cen.12691 . (PMID: 10.1111/cen.12691)
Kremidas, D, Wisniewski, T, Divino, VM, Bala, K, Olsen, M, Germak, J, et al.. Administration burden associated with recombinant human growth hormone treatment: perspectives of patients and caregivers. J Pediatr Nurs 2013;28:55–63. https://doi.org/10.1016/j.pedn.2011.12.006 . (PMID: 10.1016/j.pedn.2011.12.006)
Pampanini, V, Deodati, A, Inzaghi, E, Cianfarani, S. Long-acting growth hormone preparations and their use in children with growth hormone deficiency. Horm Res Paediatr 2023;96:553–9. https://doi.org/10.1159/000523791 . (PMID: 10.1159/000523791)
Yuen, KCJ, Miller, BS, Boguszewski, CL, Hoffman, AR. Usefulness and potential pitfalls of long-acting growth hormone analogs. Front Endocrinol 2021;12:637209. https://doi.org/10.3389/fendo.2021.637209 . (PMID: 10.3389/fendo.2021.637209)
Hwang, JS, Lee, HS, Chung, WY, Han, HS, Jin, DK, Kim, HS, et al.. Efficacy and safety of LB03002, a once-weekly sustained-release human GH for 12-month treatment in Korean children with GH deficiency. Eur J Endocrinol 2013;169:179–85. https://doi.org/10.1530/eje-13-0148 . (PMID: 10.1530/eje-13-0148)
Péter, F, Bidlingmaier, M, Savoy, C, Ji, HJ, Saenger, PH. Three-year efficacy and safety of LB03002, a once-weekly sustained-release growth hormone (GH) preparation, in prepubertal children with GH deficiency (GHD). J Clin Endocrinol Metab 2012;97:400–7. https://doi.org/10.1210/jc.2011-2234 . (PMID: 10.1210/jc.2011-2234)
Khadilkar, V, Radjuk, KA, Bolshova, E, Khadgawat, R, El Kholy, M, Desai, M, et al.. 24-month use of once-weekly GH, LB03002, in prepubertal children with GH deficiency. J Clin Endocrinol Metab 2014;99:126–32. https://doi.org/10.1210/jc.2013-2502 . (PMID: 10.1210/jc.2013-2502)
Hou, L, Huang, K, Gong, C, Luo, F, Wei, H, Liang, L, et al.. Long-term pegylated growth hormone for children with growth hormone deficiency: a large, prospective, real-world study. J Clin Endocrinol Metab 2023;108:2078–86. https://doi.org/10.1210/clinem/dgad039 . (PMID: 10.1210/clinem/dgad039)
Chung, S, Yoo, JH, Choi, JH, Rhie, YJ, Chae, HW, Kim, JH, et al.. Design of the long-term observational cohort study with recombinant human growth hormone in Korean children: LG Growth Study. Ann Pediatr Endocrinol Metab 2018;23:43–50. https://doi.org/10.6065/apem.2018.23.1.43 . (PMID: 10.6065/apem.2018.23.1.43)
Kim, JH, Yun, S, Hwang, SS, Shim, JO, Chae, HW, Lee, YJ, et al.. The 2017 korean national growth charts for children and adolescents: development, improvement, and prospects. Korean J Pediatr 2018;61:135–49. https://doi.org/10.3345/kjp.2018.61.5.135 . (PMID: 10.3345/kjp.2018.61.5.135)
Bayley, N, Pinneau, SR. Tables for predicting adult height from skeletal age: revised for use with the greulich-pyle hand standards. J Pediatr 1952;40:423–41. https://doi.org/10.1016/s0022-3476(52)80205-7 . (PMID: 10.1016/s0022-3476(52)80205-7)
Hyun, SE, Lee, BC, Suh, BK, Chung, SC, Ko, CW, Kim, HS, et al.. Reference values for serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Korean children and adolescents. Clin Biochem 2012;45:16–21. https://doi.org/10.1016/j.clinbiochem.2011.10.003 . (PMID: 10.1016/j.clinbiochem.2011.10.003)
Lamb, YN. Lonapegsomatropin: pediatric first approval. Paediatr Drugs 2022;24:83–90. https://doi.org/10.1007/s40272-021-00478-8 . (PMID: 10.1007/s40272-021-00478-8)
Lamb, YN. Somatrogon: first approval. Drugs 2022;82:227–34. https://doi.org/10.1007/s40265-021-01663-2 . (PMID: 10.1007/s40265-021-01663-2)
Sävendahl, L, Battelino, T, Højby Rasmussen, M, Brod, M, Röhrich, S, Saenger, P, et al.. Weekly somapacitan in GH deficiency: 4-year efficacy, safety, and treatment/disease burden results from REAL 3. J Clin Endocrinol Metab 2023;108:2569–78. https://doi.org/10.1210/clinem/dgad183 . (PMID: 10.1210/clinem/dgad183)
Coutant, R, Bosch Muñoz, J, Dumitrescu, CP, Schnabel, D, Sert, C, Perrot, V, et al.. Effectiveness and overall safety of NutropinAq(®) for growth hormone deficiency and other paediatric growth hormone disorders: completion of the international cooperative growth study, NutropinAq(®) European registry (iNCGS). Front Endocrinol 2021;12:676083. https://doi.org/10.3389/fendo.2021.676083 . (PMID: 10.3389/fendo.2021.676083)
Mameli, C, Orso, M, Calcaterra, V, Wasniewska, MG, Aversa, T, Granato, S, et al.. Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: a systematic review and meta-analysis. Pharmacol Res 2023;193:106805. https://doi.org/10.1016/j.phrs.2023.106805 . (PMID: 10.1016/j.phrs.2023.106805)
Maniatis, AK, Carakushansky, M, Galcheva, S, Prakasam, G, Fox, LA, Dankovcikova, A, et al.. Treatment burden of weekly somatrogon vs daily somatropin in children with growth hormone deficiency: a randomized study. J Endocr Soc 2022;6:bvac117. https://doi.org/10.1210/jendso/bvac117 . (PMID: 10.1210/jendso/bvac117)
Höybye, C, Christiansen, JS. Long-acting growth hormone. Paediatr Drugs 2013;15:427–9. https://doi.org/10.1007/s40272-013-0059-8 . (PMID: 10.1007/s40272-013-0059-8)
Christiansen, JS, Backeljauw, PF, Bidlingmaier, M, Biller, BM, Boguszewski, MC, Casanueva, FF, et al.. Research growth hormone society perspective on the development of long-acting growth hormone preparations. Eur J Endocrinol 2016;174:C1–8. https://doi.org/10.1530/eje-16-0111 . (PMID: 10.1530/eje-16-0111)
Laursen, T, Gravholt, CH, Heickendorff, L, Drustrup, J, Kappelgaard, AM, Jørgensen, JOL, et al.. Long-term effects of continuous subcutaneous infusion versus daily subcutaneous injections of growth hormone (GH) on the insulin-like growth factor system, insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH-deficient adults. J Clin Endocrinol Metab 2001;86:1222–8. https://doi.org/10.1210/jcem.86.3.7323 . (PMID: 10.1210/jcem.86.3.7323)
Blum, WF, Alherbish, A, Alsagheir, A, El Awwa, A, Kaplan, W, Koledova, E, et al.. The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders. Endocr Connect 2018;7:R212–r22. https://doi.org/10.1530/ec-18-0099 . (PMID: 10.1530/ec-18-0099)
Juul, KR, Højby Rasmussen, M, Agersø, H, Overgaard, RV. Optimal monitoring of weekly IGF-I levels during growth hormone therapy with once-weekly somapacitan. J Clin Endocrinol Metab 2021;106:567–76. https://doi.org/10.1210/clinem/dgaa775 . (PMID: 10.1210/clinem/dgaa775)
Lin, Z, Shu, AD, Bach, M, Miller, BS, Rogol, AD. Average IGF-1 prediction for once-weekly lonapegsomatropin in children with growth hormone deficiency. J Endocr Soc 2022;6:bvab168. https://doi.org/10.1210/jendso/bvab168 . (PMID: 10.1210/jendso/bvab168)
Peter, F, Savoy, C, Ji, HJ, Juhasz, M, Bidlingmaier, M, Saenger, P. Pharmacokinetic and pharmacodynamic profile of a new sustained-release GH formulation, LB03002, in children with GH deficiency. Eur J Endocrinol 2009;160:349–55. https://doi.org/10.1530/eje-08-0703 . (PMID: 10.1530/eje-08-0703)

Keywords: LG growth study; childhood growth hormone deficiency; growth hormone treatment; long-acting growth hormone; safety and effectiveness

12629-01-5 (Human Growth Hormone)
0 (Delayed-Action Preparations)

Date Created: 20241017 Date Completed: 20241202 Latest Revision: 20241202

20241204

10.1515/jpem-2024-0351

39417734