ESPE Abstracts (2018) 89 P-P1-212

Real-World Safety Data in a Cohort of Children with Noonan Syndrome Treated with GH: Final Results from NordiNet International Outcome Study (IOS) and ANSWER Program

Pétur Benedikt Júlíussona, Jovanna Dahlgrenb, M Jennifer Abuzzahabc, Birgitte Tønnes Pedersend, Sebastian Roehriche & Alicia Romanof


aDepartment of Clinical Science, University of Bergen, Bergen, Norway; bDepartment of Paediatrics, Institute of Clinical Science, University of Gothenburg, Gothenburg, Sweden; cPediatric Endocrinology and Diabetes, Children’s Minnesota, Saint Paul, MN, USA; dEpidemiology, Novo Nordisk A/S, Søborg, Denmark; eGlobal Medical Affairs, Novo Nordisk Health Care AG, Zurich, Switzerland; fDepartment of Pediatrics, New York Medical College, Valhalla, New York, NY, USA


Objectives: Current safety data do not indicate an association of GH therapy with increased risk for development/progression of tumours, or worsening of congenital cardiac conditions in individuals with Noonan syndrome (NS); however, data are limited. This report describes real-world safety data on GH therapy in paediatric patients with NS.

Methods: Two complementary non-interventional, multicentre studies, NordiNet IOS (NCT00960128) and ANSWER Program (NCT01009905), evaluated long-term effectiveness and safety of Norditropin (somatropin; Novo Nordisk A/S) as prescribed by treating physicians in a real-world clinical setting. Safety events (serious adverse events not related to therapy (SAEs), non-serious and serious adverse reactions (NSARs/SARs)) were evaluated in GH-treated patients with NS (n=412) enrolled in these studies.

Results: Baseline characteristics (% or mean (S.D.)): female, 29.1%; age at treatment start, 9.48 (3.92) years; height standard deviation score (SDS), −2.65 (0.95); weight SDS, −2.03 (1.31); IGF-I SDS, −1.13 (1.62); IGF-binding protein-3 SDS, −0.91 (1.72); GH dose (μg/kg per day), 43.9 (13.7); GH naïve (68.5%). Mean (SD) follow-up time on GH treatment, 3.1 (2.6) years and mean GH dose (μg/kg per day) during treatment, 46.6 (13.6). A total of 35 (8.5%) patients were diagnosed with cardiovascular (CV) comorbidities prior to GH start, with pulmonary valve stenosis (n=19) and atrial septal defect (n=5) being most frequent. After start of GH treatment, five patients were diagnosed with (potentially pre-existing) CV comorbidities: unspecified CV disease (n=3), ruptured abdominal aortic aneurysm (n=1), pulmonary valve stenosis (n=1). Overall, 31 safety events were reported in 21 patients (#events/#patients): NSARs, 21/15; SARs, 2/1; SAEs, 8/5. Most patients with a safety event reported one occurrence (16/21). For patients with safety events, mean (SD) age at treatment start was 9.90 (4.13) years and baseline height SDS was −3.14 (0.82). The most common NSARs were headache (six events/six patients) and arthralgia (five events/three patients). Two SARs (brain neoplasm; metastases to spine) were reported in one patient. The SAEs reported: giant cell epulis (one patient), scoliosis and spinal fusion surgery (both in one patient), moyamoya disease (one patient), glioneuronal tumour (one patient), and aggravated glioneuronal tumour and epilepsy (one patient). Glioneuronal tumours have previously been associated with Noonan syndrome and RASopathies. No cardiac safety events were reported in these patients.

Conclusions: These data suggest a favourable safety profile of GH therapy in patients with NS, including those with pre-existing cardiovascular comorbidities.

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