Dose optimization of PEG-rhGH therapy to improve growth outcomes of childhood-onset growth failure

Abstract

Background: This study evaluates the efficacy and safety of optimized PEG-rhGH dosing in pre-pubertal and pubertal children with Childhood-Onset Growth Failure due to growth hormone deficiency (GHD) or non-GHD causes.

Methods: This study employed a combined retrospective (n = 144) and prospective (n = 14) design to examine the PEG-rhGH dosing strategies' impact. A total of 158 children were enrolled in the study, of whom 130 were included in the analysis after completing a minimum of one year of follow-up. Participants were stratified into pre-pubertal and pubertal groups. PEG-rhGH therapy with dose titration was administered based on growth response and IGF-1 level. The primary goal of the study was to evaluate the effect of individualized PEG-rhGH dosing, including clinically-based target height velocity and IGF-1 titration, on height velocity in children with GHD and non-GHD small children, stratified by puberty. Outcome measures included change in height, weight, BMI, and adverse events. Data were analyzed with SPSS 25.0.

Results: Pre-pubertal children exhibited a significantly greater height increase compared to pubertal adolescents (9.75 cm vs. 9.01 cm, p = 0.0159). A dose-dependent effect on growth velocity was observed in both groups. In the pubertal group, growth velocity (GV) increased from 0.80 ± 0.20 cm/year at doses ≤0.200 mg/kg/week to 0.99 ± 0.38 cm/year at doses ≥0.220 mg/kg/week (p = 0.017). Similarly, in the pre-pubertal group, GV increased from 0.87 ± 0.23 cm/year at the lowest dose to 1.10 ± 0.24 cm/year at the highest dose (p = 0.048). These findings confirm a dose-response relationship, particularly at doses exceeding 0.200 mg/kg/week.

Conclusions: PEG-rhGH therapy was more effective in promoting height growth in pre-pubertal children compared to pubertal adolescents. A clear dose-dependent effect was observed in both groups, emphasizing the importance of individualized dosing for optimal growth outcomes.

Keywords: Childhood-onset growth failure; Dose optimization; Growth hormone deficiency (GHD); Growth hormone therapy; PEGylated recombinant human growth hormone (PEG-rhGH).