Long-term safety and effectiveness of recombinant human growth Hormone in Korean pediatric patients with growth disorders: 9-year interim analysis from LG Growth Study

초록

This study aimed to evaluate the long-term safety and effectiveness of recombinant human growth hormone (rhGH; Eutropin®, Eutropin®Pen, Eutropin®AQ, and Eutropin®Plus, LG Chem, Ltd.) treatment in Korean pediatric patients. This observational study has been conducted since 2011, and the data were collected up to August 2021 for interim analysis. The incidence rates of all adverse events (AEs) were assessed for safety analysis, and the height velocity (HV), height standard deviation score (SDS) and inulin like growth factor-1 (IGF-1) were evaluated for efficacy. During the 9-year study, a total of 4,525 patients were enrolled, and 4,442 patients (male 58.2%, female 41.8%) were analyzed for safety. Of those patients, 2,923 (65.8%) had growth hormone deficiency (GHD), 650 (14.6%) were born small for gestational age (SGA), 606 (13.6%) were diagnosed with idiopathic short stature (ISS), 253 (5.7%) had Turner syndrome (TS) and 10 (0.2%) had chronic renal failure (CRF). The mean age at the screening was 7.6 years and the mean treatment duration was 3.7 years. AEs were reported in 1,337 (30.1%) patients, most AEs were mild. A total of 34 neoplasms were reported in 30 (0.7%) patients, most were benign and/or non-related to rhGH. Cumulative results of AEs showed that the proportions of patients experiencing adverse drug reactions (ADRs), serious adverse events (SAEs), and serious adverse drug reactions (SADRs) remained relatively stable throughout 9 years of follow-up (5.8% for ADRs, 3.4% for SAEs and 0.3% for SADRs). When the effectiveness was assessed in 1,612 patients followed-up for 12 months, HV was 9.1±1.8, 9.2±1.6, 8.9±1.5, 7.4±1.8, and 8.5±1.9 cm/year in GHD, SGA, ISS, TS and CRF patients, respectively. The height SDS significantly increased from baseline to 4 years in GHD (from -2.6±0.7 to -1.1±1.1), SGA (from -2.6±0.6 to -1.1±1.1), ISS (from -2.7±0.7 to -1.8±0.9), TS (from -2.9±0.9 to -2.2±0.9) and CRF (from -2.7±1.1 to -1.6±0.7) patients, respectively. IGF-1 SDS significantly increased from −0.7±1.0 to 0.8±1.6 at 12 months and maintained within 0 to +2 SDS throughout the study period (p<0.0001). These data demonstrated the safety of long-term GH treatment in Korean pediatric patients with GHD, SGA, ISS, TS, and CRF, and there was a significant height gain during the first 4 years of follow-up in all groups. In particular, the HV improved the most after in the first year of treatment.