Comparison of actual GH dose with labeled dose in children with short stature based on the LG Growth Study

초록

Objectives: This study aimed to analyze dosing patterns of recombinant human growth hormone (rhGH) (Eutropin® Inj.., Eutropin®Pen Inj., and Eutropin®AQ Inj. for daily injection, and Eutropin®Plus Inj. for weekly injection, LG Chem, Ltd.) using the collected data of the LG Growth Study (LGS) in Korean pediatric patients with growth disorders including growth hormone deficiency (GHD), idiopathic short stature (ISS), small for gestational age (SGA), and Turner Syndrome (TS). Methods: The LGS, an open-label, multicenter (total 76 sites), observational study has begun in November 2011, and the data collected until March 2020 was used for this analysis. GH dosing was compared descriptively across indications and to labeled dose per each indication in Korea. All reported adverse events (AEs) across indications were also assessed. Also the literary comparison of GH dosing data with those from other observational studies in USA and European countries (NordiNet® IOS and ANSWER Program) was done. Results: During the 8-year study, a total of 3,813 patients were enrolled, and dosing data from total 3,590 patients were used for analysis. Of those patients, 2,328 (64.8%) had GHD, 523 (14.6%) were diagnosed with ISS, 483 (13.5%) were born SGA, and 246 (6.9%) had TS. The mean treatment duration was 3.5 years. In patients with GHD, mean GH dose of daily injection products (0.24 mg/kg/week) was slightly higher than its labeled dose (0.17 to 0.21 mg/kg/week) in Korea, and the same trend was shown in weekly injection product (0.59 mg/kg/week over the labeled dose of 0.50 mg/kg/week). But the mean doses in ISS (0.26 mg/kg/ week), SGA (0.28 mg/kg/week), and TS (0.30 mg/kg/week) were less than those corresponding labeled/recommended doses. This is similar pattern with other observational studies in USA and European countries even though their clinical practice guideline are different from Korea. Among total 1,035 subjects who reported adverse events (AEs), there were 672 (28.9%) patients in GHD, 122 (23.3%) in ISS, 123 (25.5%) in SGA, and 112 (45.5%) in TS. Most of the reported AEs were mild in severity, and 5.3% of them were related with rhGH treatment. Conclusions: In this study, GHD patients received a slightly higher doses than labeled recommendations, but patients with ISS, SGA and TS used lower doses of GH than the labeled dose. And the incidence rate of AEs was not correlated with the dosing pattern across the indications.