长效重组人生长激素治疗儿童生长激素缺乏症的有效性及安全性研究

Study on the efficacy and safety of long-acting growth hormones in treating pediatric growth hormone deficiency patients

目的比较长效聚乙二醇重组人生长激素(PEG-rhGH)和短效重组人生长激素(rhGH)治疗对生长激素缺乏症(GHD)患儿的有效性和安全性。方法 50例GHD患儿中20例给予0.2 mg/(kg·周) PEG-rhGH治疗(长效组);30例给予0.03 mg/(kg·d)短效rhGH治疗(短效组),疗程为56周。分别在治疗前、治疗后16、28、56周评价两组患儿的身高、年生长速率、身高标准差积分(HTSDS)、骨龄(BA)、血清胰岛素样生长因子1(IGF-1)及甲状腺功能、空腹血糖、空腹胰岛素、糖化血红蛋白、血脂和胰岛素抵抗(IR)。结果长效组和短效组的生长速度在治疗28周时较治疗前均显著提高(P<0.05)[长效组:(3.67±0.81)cm/年至(14.05±2.30)cm/年,短效组(3.39±1.36)cm/年至(13.63±2.32) cm/年],长效组较短效组提高更明显(t=2.114,P<0.05);治疗至56周长效组和短效组的生长速度分别为(10.98±1.01)cm/年和(10.77±1.48)cm/年,两组比较差异无统计学意义(P>0.05)。治疗第16周起两组患儿的HTSDS较治疗前出现显著改善(P<0.05),逐渐接近正常水平。从治疗第4周开始长效组HTSDS改善明显优于短效组(P<0.05),在观察过程中一直持续存在。两组患儿在治疗后IGF-1 SDS逐渐提升,至治疗16周开始较基线水平有显著提高(P<0.05)。疗程至28周开始长效组IGF-1 SDS较短效组在正常范围内显著升高,差异有统计学意义(P<0.05)。两组患儿在56周的治疗中均未见严重不良反应。结论 PEG-rhGH对儿童GHD治疗有效,效果优于短效rhGH,未见严重不良反应。

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-1 SDS gradually increased for both groups after TI,and showed significant differences from 16 weeks after TI compared with baseline(P<0.05). Additionally, IGF-1 SDS 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.