Long-term effectiveness and safety of daily growth hormone therapy in Japanese children with Noonan syndrome: a post-marketing surveillance study.

Daily GH therapy with Norditropin® improved height SDS in new patients with Noonan syndrome over the study period.

• New patients (n=35) received Norditropin® after study initiation.
• Change from baseline in mean (SD) height SDS according to Japanese standards was 1.01 (0.5) for new patients.
• Change from baseline in mean (SD) height SDS according to NS standards was 0.92 (0.3) for new patients.
• Study took place at 22 sites in Japan during November 2017–January 2022.

Daily GH therapy with Norditropin® improved height SDS in existing patients with Noonan syndrome who had previously participated in a 4-year trial.

• Existing patients (n=35) were previously enrolled in a 4-year trial of Norditropin® for NS (ClinicalTrials.gov NCT01927861).
• Change from baseline in mean (SD) height SDS according to Japanese standards was 1.01 (1.0) for existing patients.
• Change from baseline in mean (SD) height SDS according to NS standards was 1.31 (0.8) for existing patients.

The overall incidence of adverse drug reactions (ADRs) was low across both new and existing patient groups.

• Four new patients experienced five ADRs in total.
• Five existing patients experienced one ADR each.
• Total of 70 participants were enrolled and received Norditropin® at least once during the study.
• No new safety issues were identified during the study period.

Serious adverse events (SAEs) were rare, and the one death that occurred was judged unlikely to be related to Norditropin®.

• One new patient experienced one SAE.
• Three existing patients experienced one SAE each.
• One existing patient with pre-existing cardiomyopathy who experienced an SAE (arrhythmia) died during the study.
• Norditropin® causality for the death was judged 'unlikely.'

The study design was a post-marketing, prospective, non-interventional surveillance study conducted at 22 sites in Japan.

• ClinicalTrials.gov registration: NCT03435627.
• Study period: November 2017 to January 2022.
• 70 total participants enrolled, comprising 35 new patients and 35 existing patients.
• Treatment was administered as per routine clinical practice.
• Main outcome measures were adverse drug reactions (ADRs) and serious adverse events (SAEs), with height improvements also measured.

The authors recommend careful monitoring for patients with Noonan syndrome and cardiomyopathy who receive GH therapy.

• This recommendation was prompted by the death of one existing patient with pre-existing cardiomyopathy who experienced arrhythmia as an SAE.
• Norditropin® causality was judged 'unlikely' for this event.
• No new safety issues were identified across the broader study population.