ESPE Abstracts

Objectives: Mutations in PTPN11 are known to be associated with Noonan syndrome (NS), accounting for approximately 50% of cases. Data from a non-interventional and phase 3 study of Norditropin (somatropin; Novo Nordisk A/S, Denmark) were used to assess the impact of PTPN11 mutation status on growth outcomes in children with NS receiving growth hormone therapy (GHT).

Methods: The ANSWER (NCT01009905) programme is a non-interventional, multicentre, observational study conducted in the United States; GHLIQUID-4020 (NCT01927861) is a 4-year, randomised, double-blind, multicentre trial in Japanese patients. In this analysis, data from patients in these studies with clinically diagnosed NS were pooled to assess the impact of PTPN11 mutation status on growth outcomes over 4 years of GHT. Data are presented for the subgroup of patients who were GHT-naïve and prepubertal at baseline.

Results: A total of 69 patients with known PTPN11 mutation status were included in the analysis: 49 tested positive for a mutation (PTPN11-positive) and 20 were PTPN11-negative; 47 were male and 22 were female. Gene mutations identified in PTPN11-negative patients included BRAF (n = 1), KRAS (n = 1), RAF1 (n = 3), RIT1 (n = 1), SHOC2 (n = 1) and SOS1 (n = 2). Cardiovascular comorbidities were present in 55% of patients at baseline, including atrial septal defect (n = 16; 23.2% of patients), pulmonary valve stenosis (n = 9; 13.0%), pulmonary artery stenosis (n = 7; 10.1%) and hypertrophic cardiomyopathy (n = 7; 10.1%). Baseline characteristics were generally similar between PTPN11-positive and negative patients. Mean (standard deviation [SD]) age at GHT start was 6.4 (3.3) years in PTPN11-positive and 6.4 (2.5) years in PTPN11-negative patients. Mean (SD) GHT dose at baseline was 0.047 (0.015) mg/kg/day in PTPN11-positive patients and 0.054 (0.016) mg/kg/day in PTPN11-negative patients. Change from baseline in height SD score (SDS) is shown in Table 1; no significant differences between PTPN11-positive and PTPN11-negative patients were observed.

Conclusions: GHT over 4 years resulted in improved growth outcomes in GHT-naïve, prepubertal NS patients, irrespective of PTPN11 mutation status.