ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 66 P72 | DOI: 10.1530/endoabs.66.P72

Real-world safety data in children with Noonan syndrome treated with growth hormone: results from NordiNet®IOS and the Answer®Program

Pétur Júlíusson1, Jovanna Dahlgren2, Jennifer Abuzzahab3, Jo Blair4, Alberto Pietropoli5 & Alicia Romano6

1University of Bergen, Bergen, Norway; 2University of Gothenburg, Gothenburg, Sweden; 3Children’s Minnesota, Saint Paul, USA; 4Alder Hey Children’s Hospital, Liverpool, UK; 5Novo Nordisk Health Care AG, Zurich, Switzerland; 6New York Medical College, Valhalla, USA

Objective: To describe real-world safety data on growth hormone therapy (GHT) in paediatric patients with Noonan syndrome (NS) who were enrolled in NordiNet® IOS and the ANSWER®Program.

Introduction: Patients with NS have a high prevalence of cardiac defects and an increased risk for leukaemia and certain malignancies compared to the general population. Current safety data do not indicate an association of GHT with worsening of congenital cardiac defects or an increased risk for malignancies in NS patients; however, data are limited.

Methods: The long-term effectiveness and safety of Norditropin®, were evaluated in two non-interventional, multicentre studies. We report safety results for 412 paediatric patients with NS.

Results: 31 safety events were reported in 21 patients. The majority 67% (21/31) were Non-Serious Adverse Drug Reactions. Most patients experienced a single event (16/21). One patient reported two Serious Adverse Drug Reactions. Under the MedDRA term, ‘Neoplasms, benign, malignant and unspecified’, four events were reported in three patients. Cardiovascular comorbidities were reported in 35 (8.5%) patients prior to GH start. After GH start, (potentially pre-existing) cardiovascular comorbidities were reported in five patients: unspecified cardiovascular disease (n=3), pulmonary valve stenosis (n=1) and ruptured abdominal aortic aneurysm (n=1); these events were all reported as comorbidities rather than Adverse Events. No other cardiac SARs, NSARs or SAEs not related to GHT were reported.

Discussion: In the current analysis, one cardiac safety event (ruptured abdominal aortic aneurysm) was reported. A recent randomised, double-blind, clinical trial of Norditropin®, in which cardiac function was monitored (n=51), showed no evidence of a negative effect of GH on cardiac function or structure. Furthermore, previous reports indicate that long-term GHT does not appear to have negative effects on the heart, in particular, ventricular wall thickness.

Conclusions: Real-world data from NordiNet®IOS and the ANSWER® Program support a favourable safety profile of GH therapy in patients with NS, specifically regarding cardiac safety events. As with other real-world studies, some comorbidities and safety events may have been under-reported.