Background: GH treatment for ISS received first approval in the USA in 2003 based on data from two controlled clinical trials. Eligibility is restricted to those with baseline (BL) height standard deviation score (HtSDS) ≤−2.25; other approvals followed, but not in Europe.
Objective and hypotheses: To assess outcomes of GH therapy in a large cohort of patients (pts) treated in routine clinical practice.
Methods: Short-term Ht gain, final height (FHt, defined by ≥1 of closed epiphyses, Ht velocity <2 cm per year, bone age >14 years for girls/>16 years for boys) and safety were assessed using data (mean±S.D. unless stated) collected in GeNeSIS.
Results: ISS represents 13% of all enrolled pts (2833 of 22 161), 91% were from the USA, ~81% were Caucasian and 71% male. In 420 pts with up to 4 years of treatment, age at BL was 10.2±2.7 years, HtSDS was −2.4±0.7 and GH dose 0.31±0.08 mg/kg per week; ΔHtSDS was 0.6±0.3 (y1), 0.3±0.3 (y2), 0.3±0.3 (y3) and 0.1±0.3 (y4). Girls with ISS were younger at BL than boys (9.7±2.3 vs 10.4±2.8 y), shorter (HtSDS −2.7±0.7 vs −2.3±0.6), but had comparable ΔHtSDS (0.6±0.4 vs 0.6±0.3 [y1], 0.3±0.3 vs 0.3±0.2 [y2], 0.3±0.4 vs 0.3±0.3 [y3] and 0.1±0.4 vs 0.2±0.3 [y4]). FHt was available for 530 pts with age 12.3±2.5 y, BMI SDS −0.4±1.3 and HtSDS −2.4±0.8 at BL. Age, BMI SDS, FHt SDS and GH duration at FHt were 16.6±1.7 years, 0.2±1.4, −1.2±0.9 and 4.2±2.4 years, respectively. FHt gain from BL was 1.1±1.0 SDS, with 83% of pts achieving FHt >−2 SDS. FHt was greater for boys (FHt SDS −1.1±0.9, HtSDS gain 1.2±1.0) than girls (−1.4±0.9, 1.0±1.0), but boys had longer duration of therapy (4.6±2.4 vs 3.5±2.0 years). There were no significant gender differences for BL HtSDS, BMI SDS or GH dose. Of 2632 GH-treated pts with ISS with ≥1 follow-up visit (2.9±2.1 years of follow-up) ≥1 adverse event (AE) was reported for 619 (24%). AEs reported for ≥2% were headache (3%), ADHD (2%), arthralgia (2%) and scoliosis (2%); 1 death (septic meningitis), three cases of type 1 diabetes and one cancer (malignant nevus) were reported.
Conclusion: GH-treated pts with ISS had substantial Ht gain, similar to that observed in other studies and in other short stature conditions. Girls received GH less often than boys, but had similar Ht gain. No ISS-specific safety issues were identified.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology