Objective To compare the efficacy and safety betwen a weekly PEGylated human growth hormone (PEG-rhGH,Jintrolong) and a daily growth hormone in children with growth hormone deficiency (GHD),in order to provide evidence for clinical application. Methods Totally 50 GHD children were enrolled in this study,of whom 20 cases were treated with weekly PEG-rhGH [0.2 mg/(kg·week)],and the other 30 cases were treated with daily rhGH [0.03 mg/(kg·week)]. Both treatments last for 56 weeks. The height,height velocity (HV),height standard deviation score(HTSDS),serum insulin-like growth factor-1(IGF-1),thyroid function,fasting blood glucose,fasting insulin,glycated hemoglobin (HbAlc),lipids and insulin resistance(IR) of the participants was measured before treatment,16,28 and 56 weeks after treatment initiation,respectively. Results Among the patient groups receiving weekly PEG-rhGH and daily rhGH,HVs were significantly increased from (3.67±0.81)cm/year and (3.39±1.36)cm/year before treatment to (14.05±2.30)cm/year and (13.63±2.32)cm/year in 28 weeks after treatment initiation (TI) (P<0.05). A significantly greater HV increase was observed in weekly PEG-rhGH group (P<0.05). At the end of treatment (56 weeks post TI),the HVs were (10.98±1.01)cm/year and (10.77±1.48)cm/year for the groups receiving weekly PEG-rhGH and daily rhGH treatment,respectively,but with no statistically significant difference between the two groups(P>0.05). Additionally,there was significant improvement in HTSDS compared with baseline from 16 weeks after TI in two groups,and HTSDS gradually reached to normal level (P<0.05). A more significant increase was observed in the weekly PEG-rhGH group than that in the daily rhGH group in 4 weeks after TI and through the whole treatment period (P<0.05). IGF-1SDS gradually increased for both groups after TI,and showed significant differences from 16 weeks after TI compared with baseline(P<0.05). Additionally,IGF-1SDS was significantly higher in weekly PEG-rhGH group than that in daily rhGH group from 28 weeks after TI. Neither the weekly PEG-rhGH group nor the daily rhGH group experienced severe adverse event throughout the treatment period. Conclusions Weekly PEG-rhGH is effective and safe for GHD treatment,and its efficacy is superior to daily rhGH. No severe side effect is observed.
Key words
growth hormone deficiency /
weekly PEG-rhGH /
daily rhGH /
efficacy /
safety
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] 陈文君,张杰. 长效生长激素金赛增与短效生长激素赛增治疗生长激素缺乏症的对比研究[J]. 临床和实验医学杂志,2019,18(2):171-174.
[2] 中华医学会儿科学分会内分泌遗传代谢学组,《中华儿科杂志》编辑委员会. 基因重组人生长激素儿科临床规范应用的建议[J]. 中华儿科杂志,2013,51(6):426-432.
[3] Mizokami-Stout K,Cree-Green M,Nadeau KJ. Insulin resistance in type 2 diabetic youth[J].Curr Opin Endocrinol Diabetes Obes,2012,19(4):255-262.
[4] Robabeh G,Ali T. Prevalence of impaired glucose tolerance and insulin resistance among obese children and adolescents[J]. Ther Clin Risk Manag,2010,6:345-349.
[5] Turner-Bowker M,Yaworsky A,Palladino A,et al. Development and psychometric evaluation of the life interference questionnaire for growth hormone deficiency (LIQ-GHD) to assess growth hormone injection burden in children and adults[J]. Patient,2020,13:289-306.
[6] Wilson TA,Rose SR,Cohen P,et al. Update of guidelines for the use of growth hormone in children:The Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee[J]. J Pediatr,2003,143(4):415-421.
[7] Yuen KCJ,Miller BS,Biller BMK.The current state of long-acting growth hormone preparations for growth hormone therapy[J]. Curr Opin Endocrinol,2018,25(4):267-273.
[8] Baxter L,Bryant J,Cave CB,et al. Recombinant growth hormone for children and adolescents with Turner syndrome[J]. Cochrane DBSyst Rev,2007,(1):Art. No.:CD003887.
[9] Alexandraki KI,Grossman AB. Management of Hypopituitarism[J]. J Clin Med,2019,5(8):2153-2176.
[10] Vimalachandra D,Hodson EM,Willis NS,et al. Growth hormone for children with chronic kidney disease[J]. Cochrane DB Syst Rev,2006,(3):Art. No.:Cd003264.
[11] Høybye C,Cohen P,Hoffman AR,et al. Status of long-acting-growth hormone preparations-2015[J]. Growth Horm IGF Res,2015,25(5):201-206.
[12] Luo XP,Hou L,Liang L,et al. Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency:phase II and phase III multicenter,randomized studies[J]. Eur J Endocrinol,2017,177:195-205.
[13] Saenger PH,Mejia-Corletto J. Long-acting growth hormone:an update[J]. Endocr Dev Basel Karger,2016,30:79-97.
[14] Yang YY,Bai X,Yuan XX,et al. Efficacy and safety of long-acting growth hormone in children with short stature:a systematic review and meta-analysis[J].Endocrine,2019,65:25-34.
[15] 和凡,钟国平,肖楚等. ELISA法研究聚乙二醇重组人生长激素注射液单次给药人体药代动力学[J]. 国际医药卫生导报,2017,23(11):1699-1702.
[16] Grimberg A,DiVall SA,Polychronakos C,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[J]. Horm Res Paediatr,2016,86(6):361-397.
[17] Palmieri VV,Lonero A,Bocchini S,et al. Uniparental disomy and pretreatment IGF-1 may predict elevated IGF-1 levels in Prader-Willi patients on GH treatment[J]. Growth Horm IGF Res,2019,48-49:9-15.
[18] Hwang JS,Lee HS,Lee KH,et al. Once-weekly administration of sustained-release growth hormone in Koreanprepubertal children with idiopathic short stature:a randomized,controlled phase Ⅱ study[J]. Horm Res Paediatr,2018,90(1):54-63.
[19] Zelinska N,Iotova V,Skorodok J,et al.Long acting C-terminal peptide-modified hGH (MOD-4023):Results of a safety and dose-finding study in GHD children[J]. J Clin Endocrinol Metab,2017,102(5):1578-1587.
[20] Chatelain P,Malievskiy O,Radziuk K,et al. A randomized phase 2 study of long-acting transcon GH vs daily GH in childhood GH deficiency[J]. J Clin Endocrinol Metab,2017,102(5):1673-1682.
[21] Khadlikar V,Radjuk KA,Bolshova E,et al. 24-month use of once-weekly GH,LB03002,in prepubertal children with GH deficiency[J]. J Clin Endocrinol Metab,2014,99:126-132.
[22] Canete MD,Valle-Martos R,Martos R,et al. Effects of growth hormone therapy on metabolic parameters,adipokine and endothelial dysfunction in prepuberal children[J]. Acta Paediatr,2019,5(13):2027-2033.
PDF(461 KB)
