Dose optimization and safety of long-acting pegylated growth hormone in pubertal idiopathic short stature: A retrospective real-world group study

Purpose Given the lack of established dosing strategies for polyethylene glycol recombinant long-acting human growth hormone (PEG-rhGH) in pubertal patients with idiopathic short stature (ISS), it is necessary to develop optimal dosing regimens. This study aims to explore relevant clinical and prognostic factors influencing the efficacy of PEG-rhGH in pubertal ISS patients, and to evaluate the efficacy and safety of higher-dose PEG-rhGH. Methods A retrospective real-world group study analyzed efficacy and safety data from 118 children with ISS treated with PEG-rhGH . Results Following 12 months of PEG-rhGH treatment in children with ISS:① Pre-pubertal demonstrated significantly greater gain in height standard deviation score (HtSDS) and higher height velocity(HV) than the pubertal group (ΔHtSDS: 0.98 ± 0.47 vs. 0.52 ± 0.33, p < 0.001; HV: 10.65 ± 1.55 cm/year vs. 9.98 ± 1.76 cm/year, p = 0.035).②The high-dose group showed significantly greater gain in HtSDS and higher HV compared to the low-dose group (ΔHtSDS: 0.98 ± 0.45 vs. 0.62 ± 0.42, p < 0.001; HV: 11.99 ± 1.25 cm/year vs. 9.69 ± 1.43 cm/year, p < 0.001).③HtSDS gain exhibited a dose-dependent effect with PEG-rhGH treatment. ④The high-dose group did not exhibit additional treatment-emergent adverse events (TRAEs) compared to the low-dose group. Conclusion Pubertal constitutes a negative predictive factor for PEG-rhGH efficacy in children with ISS, and the efficacy of PEG-rhGH is dose-dependent. Therefore, higher dose (≥0.23 mg/kg/week) of PEG-rhGH treatment is beneficial to enhance the efficacy of pubertal ISS patients. No serious adverse events were observed. What is known • Polyethylene glycol recombinant long-acting human growth hormone (PEG-rhGH) significantly enhances growth outcomes in children with idiopathic short stature through weekly injections, while maintaining a favorable safety profile, representing an important advancement in long-term therapy. • The use of PEG-rhGH in pubertal children with ISS is still an area of uncertainty. What is new • Pubertal constitutes a negative predictive factor for PEG-rhGH efficacy in children with ISS. • Increasing the dose of PEG-rhGH is beneficial for counteracting the adverse effects on efficacy caused by puberty. • Increasing the dose of PEG-rhGH did not cause additional adverse effects.