Comparative evaluation of short-term biomarker response to treatment for growth hormone deficiency in Chinese children with growth hormone deficiency born small for or appropriate for gestational age: a randomized phase IV open-label study

Abstract

Objectives: To compare the response between Chinese children with growth hormone deficiency (GHD) born either small for gestational age (SGA) or appropriate for gestational age (AGA) after 4 weeks of recombinant human growth hormone (r-hGH) therapy.

Methods: This was a phase IV, open-label, multicenter, interventional study (NCT01187550). Prepubertal children with GHD received open-label treatment with daily r-hGH (0.033 mg/kg) for 4 weeks. Serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP3), and metabolic markers (including fasting glucose, insulin, total cholesterol, and homeostasis model assessment of insulin resistance) were assessed at baseline and after 4 weeks of treatment, and were analyzed according to patient subgroup (SGA or AGA).

Results: A total of 205 children with GHD (mean age 10.4 years; 175 AGA, 30 SGA) were included in the analysis. Mean baseline serum IGF-I and IGFBP3 standard deviation scores (SDS) across the whole patient population were lower than the population norms (mean values: -2.1 SDS for IGF-I and -1.2 SDS for IGFBP3), with no significant differences between the two patient subgroups. After 4 weeks, IGF-I and IGFBP3 levels increased by 1.0 SDS (p < 0.001) and 0.34 SDS (p < 0.001), respectively, but no significant differences were found between the two patient subgroups for growth-related or metabolic markers.

Conclusions: For children with GHD born SGA, IGF-I and IGFBP3 are short-term biomarkers of responsiveness to treatment with growth hormone, as for children with GHD born AGA.

Keywords: biomarker response; insulin-like growth factor I; insulin-like growth factor-binding protein 3; recombinant human growth hormone.

Figure 1.

Patient flow diagram. *Of these 14 study withdrawals, 8 did not receive at least one dose of recombinant human growth hormone; ^$bronchitis and headache. AGA, appropriate for gestational age; ITT, intent-to-treat; PP, per protocol; SGA: small for gestational age.

Figure 2.

Growth-related biomarkers in children with growth hormone deficiency born appropriate for gestational age and small for gestational age at baseline and after 4 weeks of treatment with recombinant human growth hormone: (a) insulin-like growth factor I standard deviation score; (b) insulin-like growth factor-binding protein 3 standard deviation score. Individual patient values for growth-related biomarkers are shown for each patient subgroup/time point. Median values are indicated by the line within each dataset. IGF-I, insulin-like growth factor I; IGFBP3, insulin-like growth factor-binding protein 3; SDS, standard deviation score.