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

Reports on long-term safety and effectiveness of daily GH replacement therapy in Japanese children with short stature due to Noonan syndrome (NS) are limited. This post-marketing, prospective, non-interventional study (ClinicalTrials.gov NCT03435627) evaluated the long‑term safety and effectiveness of daily GH therapy in this patient population. The study took place at 22 sites in Japan during November 2017-January 2022. Seventy participants were enrolled and received Norditropin^® at least once during the study as per routine clinical practice: new patients (n = 35) received Norditropin^® (somatropin) after study initiation and existing patients (n = 35) were previously enrolled in a 4-year trial of Norditropin^® for NS (ClinicalTrials.gov NCT01927861). The main outcome measures were adverse drug reactions (ADRs) and serious adverse events (SAEs). Improvements in height were also measured. In total, four new patients experienced five ADRs and one new patient experienced one SAE. Five existing patients experienced one ADR each and 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 was judged 'unlikely.' Change from baseline in mean (SD) height standard deviation score (SDS), according to Japanese and NS standards, was 1.01 (0.5) and 0.92 (0.3) for new patients and 1.01 (1.0) and 1.31 (0.8) for existing patients, respectively. Our results show that Norditropin^® effectively improved height outcomes in Japanese children with NS and was well tolerated with no new safety issues identified. For patients with NS and cardiomyopathy receiving GH therapy, careful monitoring is advised.