Supplementary Material for: Long-acting PEGylated Growth Hormone in Children with Idiopathic Short Stature: 2-Year Results

Background: Idiopathic short stature (ISS) is characterized by short stature without identifiable underlying disorders. Long-acting PEGylated recombinant human growth hormone (PEG-rhGH) has emerged as a promising treatment option for ISS children. Objective: To evaluate the efficacy and safety of weekly PEG-rhGH in ISS children during the extension study. Methods: This multicenter, open-label, uncontrolled extension study (extension phase) followed the initial 52-week trial (main phase). All subjects received once-weekly PEG-rhGH at 0.2 mg/kg/wk with dose adjustment (up to 0.4 mg/kg/wk) based on height velocity (HV) and insulin-like growth factor-1 (IGF-1) standard deviation score (SDS). The primary endpoint was change in height SDS (ΔHT SDS) from baseline; secondary endpoints mainly included HV, changes in bone age/chronological age ratio, IGF-1 SDS and average annual prescribed dose. Safety was evaluated through adverse events and clinical findings. Results: Of 280 children enrolled in extension study, 268 completed 52-week treatment. This analysis included results up to week 104, representing 52-week extension phase following the 52-week main phase. At week 104, the least squares means (LSM) of ΔHT SDS were 1.517, 1.242 and 1.067 for PEG-rhGH 0.2/0.2 mg/kg/wk, 0.1/0.2 mg/kg/wk and 0/0.2 mg/kg/wk groups, respectively. The 0.2/0.2 mg/kg/wk group maintained significantly greater height improvements. HV was highest in the 0/0.2 mg/kg/wk group (9.158±1.334 cm/year), reflecting typical first-year catch-up growth. Mean IGF-1 SDS remained within 2SDS during 2 years. Conclusion: Once-weekly PEG-rhGH in children with ISS showed sustained efficacy over 2 years in all assessed height-based outcomes. Treatment remained safe and well-tolerated with no new safety signals.