Clinical evaluation of recombinant human growth hormone injection in children with growth hormone deficiency

Abstract

Recombinant human growth hormone (rhGH) has been widely used in the clinical treatment of growth hormone deficiency. To simplify the injection process and increase drug compliance, application of the GH injection has become a new treatment plan in recent years. The purpose of the current study was to evaluate the efficacy and safety of rhGH injection for the treatment of growth hormone deficiency (GHD) in children in China. In a nationwide, noncomparative, prospective, randomized, open trial, 31 children with confirmed complete GHD received subcutaneous injection of rhGH at 0.25 mg/kg·wk (0.107 IU/kg·d). The injection was given daily and the total weekly amount was separated into 6-7 injections. The patients were followed up at 3-month intervals and the treatment duration was 12 months. The height (HT), annual growth velocity (GV), mean height standard deviation score (HT SDS), blood serum insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and bone maturity before and after treatment were compared, and the safety of the treatment was analyzed. The mean HT, GV, and HT SDS were increased from 109.0±14 cm, 2.7±0.9 cm/yr, and -4.62±1.46 at baseline to 121.8±13.4 cm, 12.9±3.3 cm/yr, and -2.47±1.86 after 12 months of treatment, respectively (P<0.001). At the same time, blood IGF-I and IGFBP-3 were increased significantly [41.27±64.43 μg/L vs 159.21±167.92 μg/L and 1540.00±1325.11 mg/L vs 3533.93±1413.82 mg/L, respectively (P<0.001)]. The bone age assessments performed 6 and 12 months after the treatment showed that no advanced bone maturation was noted. No serious adverse events occurred during the treatment, and the drug-related adverse events were mainly decreased thyroid function. We conclude that rhGH injection is a safe and effective drug for treatment of growth hormone deficiency in children.

Keywords

recombinant human growth hormone / injection / growth hormone deficiency

References

[1] WiltonP,WidlundL,GuilbaudO. Bioequivalence of genotropin and somatonorm. Acta Paediatr Scand Suppl, 1987, 337: 118–121

[2] BrämswigJ H,SchlösserH,KieseK. Final height in children with growth hormone deficiency. Horm Res, 1995, 43(4): 126–128

[3] De LucaF,MaghnieM,ArrigoT,LombardoF,MessinaM F,BerasconiS. Final height outcome of growth hormone-deficient patients treated since less than five years of age. Acta Paediatr, 1996, 85(10): 1167–1171

[4] BlethenS L,BaptistaJ,KuntzeJ,FoleyT,LaFranchiS,JohansonA. Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. J Clin Endocrinol Metab, 1997, 82(2): 418–420

[5] BirnbacherR,RiedlS,FrischH. Long-term treatment in children with hypopituitarism: pubertal development and final height. Horm Res, 1998, 49(2): 80–85

[6] MacGillivrayM H,BlethenS L,BuchlisJ G,ClopperR R,SandbergD E,ConboyT A. Current dosing of growth hormone in children with growth hormone deficiency: how physiologic? Pediatrics, 1998, 102(Suppl 2): 527–530

[7] GrumbachM M,Bin-AbbasB S,KaplanS L. The growth hormone cascade: progress and long-term results of growth hormone treatment in growth hormone deficiency. Horm Res, 1998, 49(Suppl 2): 41–57

[8] AugustG P,JuliusJ R,BlethenS L. Adult height in children with growth hormone deficiency who are treated with biosynthetic growth hormone: the National Cooperative Growth Study experience. Pediatrics, 1998, 102(Suppl 2): 512–516

[9] CutfieldW,LindbergA,Albertsson-WiklandK,ChatelainP,RankeM B,WiltonP. Final height in idiopathic growth hormone deficiency: the KIGS experience. Acta Paediatr Suppl, 1999, 88(428): 72–75

[10] BernasconiS,ArrigoT,WasniewskM,GhizzoniL,RuggeriC,Di PasqualeG,VotteroA,De LucaF. Long-term results with growth hormone therapy in idiopathic hypopituitarism. Horm Res, 2000, 53(Suppl 1): 55–59

[11] BierichJ R. Multicentre clinical trial of authentic recombinant somatropin in growth hormone deficiency. Acta Paediatr Scand Suppl, 1987, 337: 135–140

[12] HuY M,JiangZ F.Zhu Futang Practical Pediatrics. 7th ed. Beijing: People’s Health Publishing House,2002, 27–34 (in Chinese)

[13] Guidelines for the use of growth hormone in children with short stature. A report by the Drug and Therapeutics Committee of the Lawson and Wilkins Pediatric Endocrine Society. J Pediatr, 1995, 127(6): 857–867

[14] RosenfeldR G,Albertsson-WiklandK,CassorlaF,FrasierS D,HasegawaY,HintzR L, LafranchiS,LippeB,LoriauxL,MelmedS,PreeceM A,RankeM B,ReiterE O,RogolA D, UnderwoodL E,WertherG A. Diagnostic controversy: the diagnosis of childhood growth hormone deficiency revisited. J Clin Endocrinol Metab, 1995, 80(5): 1532–1540

[15] RappaportR,MugnierE,LimoniC,CrosnierH,CzernichowP,LegerJ,LimalJ M, RochiccioliP,SoskinS. A 5-year prospective study of growth hormone (GH)-deficient children treated with GH before the age of 3 years. French Serono Study Group. J Clin Endocrinol Metab, 1997, 82(2): 452–456

[16] RootA W,KempS F,RundleA C,DanaK,AttieK M. Effect of long-term recombinant growth hormone therapy in children-the National Cooperative Growth Study, USA, 1985-1994. J Pediatr Endocrinol Metab, 1998, 11(3): 403–412

[17] ReiterE O,PriceD A,WiltonP,Albertsson-WiklandK,RankeM B. Effect of growth hormone treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database. J Clin Endocrinol Metab, 2006, 91(6): 2047–2054

[18] BryantJ,CaveC,MihaylovaB,ChaseD,McIntyreL,GerardK,MilneR. Clinical effectiveness and cost-effectiveness of growth hormone in children: a systematic review and economic evaluation. Health Technol Assess, 2002, 6(18), 1–175

[19] RankeM B,PriceD A,ReiterE O, eds. Growth hormone therapy in pediatrics—20 years of KIGS. Basel, Switzerland: Karger,2007, XV

[20] BlethenS L,AllenD B,GravesD,AugustG,MoshangT,RosenfeldR. Safety of recombinant deoxyribonucleic acidderived growth hormone: The National Cooperative Growth Study Experience. J Clin Endocr Metab, 1996, 81(5): 1704–1710

[21] MüllerJ,SkakkebaekN E,JacobsenB B,KellerE,HeinrichU,HartmannK, Hokken-KoelegaA C,Delemarre van de WaalH A. Norditropin SimpleXx: a liquid human growth hormone formulation, a pen system and an auto-insertion device. Horm Res, 1999, 51(Suppl 3): 109–112

[22] IyodaK,MoriwakeT,SeinoY,NiimiH. The clinical usefulness of liquid human growth hormone (hGH) (Norditropin® SimpleXxTM) in the treatment of GH deficiency. Horm Res, 1999,51(suppl 3): 113–115

[23] PeterkovaV,ArslanogluI,Bolshova-ZubkovskayaE,RomerT,ZdravkovicD,KratzschJ,JiH J,SavoyC,SaengerP. A randomized, double-blind study to assess the efficacy and safety of valtropin, a biosimilar growth hormone, in children with growth hormone deficiency. Horm Res, 2007, 68(6): 288–293

[24] RomerT,PeterF,SaengerP,StarzykJ,KoehlerB,KormanE,WalczakM,WasikR,Ginalska-MalinowskaM,SolyomE,BerghoutA. Efficacy and safety of a new ready-to-use recombinant human growth hormone solution. J Endocrinol Invest, 2007, 30(7): 578–589

[25] Ogilvy-StuartA L. Safety of growth hormone after treatment of a childhood malignancy. Horm Res, 1995, 44(Suppl 3): 73–79

[26] NgS T,ZhouJ,AdesanyaO O,WangJ,LeRoithD,BondyC A. Growth hormone treatment induces mammary gland hyperplasia in aging primates. Nat Med, 1997, 3(10): 1141–1144

[27] ScirèG,Del BiancoC,SpadoniG L,CianfaraniS. Growth hormone therapy does not alter the insulin-like growth factor-I/insulin-like growth factor binding protein-3 molar ratio in growth hormone-deficient children. J Endocrinol Invest, 2008, 31(2): 153–158

[28] RankeM B,TrauneckerR,MartinD D,SchweizerR,SchwarzeC P,WollmannH A,BinderG. IGF-I and IGF binding protein-3 levels during initial GH dosage step-up are indicators of GH sensitivity in GH-deficient children and short children born small for gestational age. Horm Res, 2005, 64(2): 68–76

[29] OyarzabalM,AliagaM,ChuecaM,EcharteG,UliedA. Multicentre survey of compliance with growth hormone therapy: what can be improved? Acta Pædiatr, 1998, 87(4): 387–391

[30] PortesE S,OliveiraJ H,MacCagnanP,AbuchamJ.Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children. Clin Endocrinol (Oxf), 2000, 53(2): 183–189

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg