Cardiovascular safety of growth hormone treatment in Noonan syndrome: real-world evidence

Abstract

Objective: The study aims to assess the cardiovascular safety of growth hormone (GH) treatment in patients with Noonan syndrome (NS) in clinical pra ctice. Design: The study design involves two observational, multicentre studies (NordiNet® IOS and the ANSWER Program) evaluating the long-term effectiveness a nd safety of GH in >38,000 paediatric patients, of which 421 had NS. Methods: Serious adverse events, serious adverse reactions (SARs) and non-serious adverse reactions (NSARs) were reported by the treating physici ans. Cardiovascular comorbidities at baseline and throughout the studies were also recorded. Results: The safety analysis set comprised 412 children with NS (29.1% females), with a mean (s.d.) baseline age of 9.29 (3.88) years, treated with an average GH dose of 0.047 (0.014) mg/kg/day during childhood. Cardiovascular comorbidities at baseline were reported in 48 (11.7%), most commonly pulmonary valve sten osis (PVS) and atrial septal defects. Overall, 22 (5.3%) patients experienced 34 safe ty events. The most common were the NSARs: headache (eight events in seven patients ) and arthralgia (five events in three patients). Two SARs occurred in one patien t (brain neoplasm and metastases to spine). No cardiovascular safety events were reco rded in patients with NS. Five cardiovascular comorbidities in five patients were repo rted after initiation of GH treatment: three cases of unspecified cardiovascular disease, on e ruptured abdominal aortic aneurysm and one PVS. Conclusions: GH treatment had a favourable safety profile in patients with NS, including those with cardiovascular comorbidities. Prospective studies are warranted to systematically assess the safety of GH treatment in patients with NS and cardiovascular disease.

Keywords

• growth hormone
• hypertrophic cardiomyopathy
• noonan syndrome
• pulmonary valve stenosis
• real-world data