Abstract 7: Use of growth hormone therapy in short patients born small for gestational age: Data from real-life French clinical practice

Background: A national French registry was created to address the absence of data on final height and safety following long-term exposure to supraphysiological doses of growth hormone (GH) in children born small for gestational age (SGA). Methods: This observational, non-interventional study (NCT01578135) included GH-naïve and non-naïve SGA children treated with GH at 126 sites in France. The inclusion period was 2005–2010 with follow-up until 2018 or until final adult (FA) height (height velocity <2 cm/year). The primary endpoints were proportion of patients with normal (>–2) height standard deviation score (HSDS) at last visit, and with normal FA HSDS. Secondary endpoints included change from baseline in HSDS and safety. Multivariate logistic regression analysis with stepwise elimination was used to identify factors associated with achieving normal HSDS. Results: Of the 1408 registered patients, every fifth child was randomly selected (n = 291) for inclusion in this long-term follow-up study. For the full population and subpopulation, mean (SD) baseline age was 8.79 (3.53) and 8.08 (3.32) years; HSDS was –2.55 (0.95) and –3.07 (0.86); 48.4% and 46.0% were female, respectively. Normal HSDS was reached in 193/291 children (66.3%). Among the 24.7% of patients who achieved FA height at last visit, 66.7% had FA HSDS >–2. Mean change from start of treatment to last visit in HSDS was +1.35 (0.97). Factors associated with reaching normal HSDS were baseline HSDS (taller better; odds ratio [95% confidence interval]: 5.65 [3.22;9.92], P < 0.0001); age at treatment start (younger better; 0.88 [0.79;0.98], P=0.0166); treatment duration excluding discontinuation periods (longer better; 1.20 [1.04;1.38], P=0.0166); and absence of a chronic disease (0.43 [0.21;0.87], P=0.0188). The majority (70.0%) of adverse events (AEs) were non-serious; 39.0% of all AEs and 7.0% of serious AEs were considered possibly/probably related to GH treatment. The most common AEs (% of patients) were increased insulin-like growth factor-I (IGF-I; 17.2%), headache (9.3%) and arthralgia (4.5%). Sixteen patients (5.5%) discontinued treatment prematurely, most commonly because of increased IGF-I (n = 4). One malignant tumour (nephroblastoma) with a fatal outcome was reported and considered unrelated to GH treatment. Conclusions: GH therapy was effective in most short children born SGA. No new safety concerns were observed. The likelihood of achieving normal HSDS with GH therapy increased with greater baseline HSDS, longer duration of GH treatment, absence of a chronic disease and younger baseline age, reinforcing the importance of early identification and treatment of short patients born SGA.