Long-term safety and efficacy of daily recombinant human growth hormone treatment in Japanese short children born small for gestational age: final report from an open and multi-center study

Abstract

Abstract.Our study aimed at evaluating the safety and efficacy of GH treatment up to near adult height (NAH) for short children born small for gestational age (SGA). This was a multi-center, open-label, long-term extension study after a one-year, randomized, open-label, dose-response study. The primary objective was to assess safety, determined by adverse events and laboratory test parameters. Height parameters were evaluated as a secondary objective. The final data after all patients completed the study were reported. Overall, 61 patients were enrolled in the study. GH treatment was well tolerated. No notable changes in HbA1c levels, oral glucose tolerance tests and glucose metabolism were observed. No new safety concerns related to long-term treatment up to NAH were identified. Twenty patients (11 boys and 9 girls) reached NAH with a mean height of 159.1 cm and 146.9 cm, respectively. The mean change in height SDS from baseline to NAH was +1.9 in boys and +1.8 in girls. Long-term GH treatment for SGA short stature was confirmed to be safe and effective for the normalization of adult height.

The long-term safety and effectiveness of growth hormone treatment in Japanese children with short stature born small for gestational age

“…The lower mean IGF I SDS following initiation of GH treatment reported in our study when compared with those reported by Tanaka et al. ( 13 ) may reflect the under-dosing of GH and it is possible that higher doses of GH could have produced more pronounced improvements in height outcomes. There may also be differences in the IGF I response associated with GH treatment in children born SGA depending on the etiology of their condition and whether or not they are GH deficient ( 33 ).…”

“…These data are reassuring and do not suggest an inappropriate increase in IGF I SDS. An increase in IGF I SDS to approximately +2 after the start of GH treatment was reported by Tanaka et al ( 13 ). The lower mean IGF I SDS following initiation of GH treatment reported in our study when compared with those reported by Tanaka et al.…”

“…Mean age at the start of GH treatment for the naïve children who achieved NAH was 10.8 yr and the mean duration of GH treatment was 4.29 yr. As the median (range) age at the start of treatment for the whole population of naïve children was 4.0 (3.0–14.0), only those children in the naïve group who were at the upper end of the age range (10 yr or older) at the start of treatment achieved NAH. Therefore, the results of the NAH SDS for naïve children obtained in our study may not be applicable in clinical practice as most children born SGA start GH treatment at a young age ( 13 ). Furthermore, in the naïve children who achieved NAH, the mean age of pubertal onset was 13.2 yr for boys and 11.4 yr for girls.…”

“…However, all mean values in the study remained within the normal range. In another study involving 61 children with short stature born SGA, HbA1c levels remained within the normal range for up to 15 yr of GH treatment (0.47 mg/kg/wk) ( 13 ). Previous studies have suggested that there is a decrease in insulin sensitivity which occurs during puberty that compensates for the increase in insulin secretion ( 29 ).…”

“…Other studies have reported mean NAH SDS of –1.2 ± 0.7 (7) and –1.4 to –1.9 ( 41 ), while a meta-analysis of randomized controlled studies conducted up to the attainment of adult height involving 391 GH-treated children born SGA reported that the mean height gained to adult height was 1.5 SD in treated children when compared with 0.25 SD in untreated children ( 42 ). In Japanese children, Tanaka et al ( 13 ) reported a mean NAH SDS of –1.6, representing a mean change in height SDS from baseline to NAH of +1.9 in boys and +1.8 in girls. Our results are therefore comparable to previous reports.…”