Participatory Study to Explore Healthcare Professionals' Perceptions of a Connected Digital Solution for Adherence Monitoring of Recombinant Human Growth Hormone Treatment: Study Protocol and First Findings.

Adherence to recombinant human growth hormone (r-hGH; somatropin, [Saizen®], Merck Healthcare KGaA, Darmstadt, Germany) treatment is fundamental to achieve positive growth outcomes in children with growth disorders and to improve quality of life and cardiometabolic risk in adult patients affected by GH deficiency. Pen injector devices are commonly used to deliver r-hGH but, to the authors' knowledge, none is currently digitally connected. Since digital health solutions are rapidly becoming valuable tools to support patients to adhere to treatment, the combination of a pen injector connected to a digital ecosystem to monitor treatment adherence is an important advance. Here, we present the methodology and first results of a participatory workshop that assessed clinicians' perceptions on such a digital solution - the aluetta™ smartdot™ (Merck Healthcare KGaA, Darmstadt, Germany) - combining the aluetta™ pen injector and a connected device, components of a comprehensive digital health ecosystem to support pediatric patients receiving r-hGH treatment. The aim being to highlight the importance of collecting clinically meaningful and accurate real-world adherence data to support data-driven healthcare.

Real-life long-term efficacy and safety of recombinant human growth hormone therapy in children with short stature homeobox-containing deficiency.

Objective: This Italian survey aims to evaluate real-life long-term efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy. Design and methods: This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3 and T4) and at near-final height (nFH) (T5), when available. Results: One hundred and seventeen SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33 years (74% prepubertal), 99 completed the first year of treatment and 46 reached nFH. During rhGH therapy, growth velocity (GV), standard deviation score (SDS) and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14 ± 0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (ß = -0.31, P = 0.030) and the GV during the first year of rhGH treatment (ß = 0.45, P = 0.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported. Conclusions: Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype. Significance Statement: Among children with idiopathic short stature, the prevalence of SHOX-D is near to 1/1000-2000 (1.1-15%) with a wide phenotypic spectrum. Current guidelines support rhGH therapy in SHOX-D children, but long-term data are still few. Our real-life data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless of the wide variety of genotypes. Moreover, rhGH therapy seems to blunt the SHOX-D phenotype. The response to rhGH in the first year of treatment and the age when rhGH was started significantly impact the height gain.