Developing the First Pragmatic Dose Conversion Between Long-Acting and Daily Growth Hormone in Prepubertal Children With Idiopathic Short Stature: A Joint Modeling Method Using Real-World Data in China
Author(s)
Xiaoping Luo, MD1, Chunxiu Gong, MD2.
1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 2Beijing Children’s Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 2Beijing Children’s Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
OBJECTIVES: To establish a clinically applicable dose conversion model between long-acting PEGylated growth hormone (LAGH) and daily growth hormone (DGH) for prepubertal children with idiopathic short stature (ISS).
METHODS: A real-world registry database of Chinese prepubertal ISS children (girls <8 years, boys <9 years; bone age delay <1 year) was analyzed. Participants were stratified by LAGH or DGH treatment. Linear regression models predicting 1-year height velocity (HV) were developed using baseline covariates: age, height SDS, bone age-chronological age (BA-CA) difference, and initial GH dose for both LAGH and DGH groups independently. Dose conversion equations were derived by equating HV predictions between formulations and further simplified using population median values.
RESULTS: A total of 5020 patients were included (LAGH: 1545; DGH: 3475). The regression equation for the DGH group is: HV = 10.388 + 7.182 × DGH dose - 0.384 × Age + 0.003 × Height SDS + 0.109 × (BA-CA). For the LAGH group, the equation is: HV = 10.103 + 6.023 × LAGH dose - 0.406 × Age - 0.177 × Height SDS + 0.148 × (BA-CA). Both models demonstrated a significant relationship between HV and the included variables (p<0.05 for most coefficients). The derived formula for dose conversion is as follows: LAGH dose = [7.182 × DGH dose + 0.285 + 0.022 × Age + 0.180 × Height SDS - 0.039 × (BA-CA)] / 6.023. Simplification of this formula, using median values for the coefficients from the dataset with external calibration, yielded a practical conversion equation: LAGH dose = [7.182 × DGH dose + 0.393] / 6.023.
CONCLUSIONS: This joint modeling method provides the first dose conversion model for LAGH and DGH in prepubertal ISS patients using large-scale real-world data. The conversion equation accounts for key clinical variables and real-world dosing practices, and also offers a simplified practical tool for therapeutic efficacy.
METHODS: A real-world registry database of Chinese prepubertal ISS children (girls <8 years, boys <9 years; bone age delay <1 year) was analyzed. Participants were stratified by LAGH or DGH treatment. Linear regression models predicting 1-year height velocity (HV) were developed using baseline covariates: age, height SDS, bone age-chronological age (BA-CA) difference, and initial GH dose for both LAGH and DGH groups independently. Dose conversion equations were derived by equating HV predictions between formulations and further simplified using population median values.
RESULTS: A total of 5020 patients were included (LAGH: 1545; DGH: 3475). The regression equation for the DGH group is: HV = 10.388 + 7.182 × DGH dose - 0.384 × Age + 0.003 × Height SDS + 0.109 × (BA-CA). For the LAGH group, the equation is: HV = 10.103 + 6.023 × LAGH dose - 0.406 × Age - 0.177 × Height SDS + 0.148 × (BA-CA). Both models demonstrated a significant relationship between HV and the included variables (p<0.05 for most coefficients). The derived formula for dose conversion is as follows: LAGH dose = [7.182 × DGH dose + 0.285 + 0.022 × Age + 0.180 × Height SDS - 0.039 × (BA-CA)] / 6.023. Simplification of this formula, using median values for the coefficients from the dataset with external calibration, yielded a practical conversion equation: LAGH dose = [7.182 × DGH dose + 0.393] / 6.023.
CONCLUSIONS: This joint modeling method provides the first dose conversion model for LAGH and DGH in prepubertal ISS patients using large-scale real-world data. The conversion equation accounts for key clinical variables and real-world dosing practices, and also offers a simplified practical tool for therapeutic efficacy.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO70
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity), Pediatrics