Abstract
Disclosure: B.S. Miller: Ascendis Pharma, BioMarin, Bristol Myers Squibb, EMD Serono, Endo Pharmaceuticals, Novo Nordisk, Pfizer, Provention Bio, Tolmar, Alexion, Abbvie, Aeterna Zenta, Amicus, Foresee Pharmaceuticals, Lumos Pharma, Lysogene, Novo Nordisk, OPKO Health, Pfizer, Prevail Therapeutics and Sangamo Therapeutics. C. Barbus: None. A. Forsythe: None. M.D. Evans: None. A. Olson: None.
Background: Current standard of care for children with growth hormone (GH) deficiency (GHD) is GH replacement therapy (GHRT) with daily GH (DGH); however, efficacy is at times hindered by difficulties maintaining adherence. Once-weekly long-acting GH (LAGH) has been developed to improve adherence through reduced injection frequency, ultimately maximizing the efficacy of GHRT. Whether this desired effect truly exists has yet to be documented. This study aims to analyze the level of adherence to GHRT and clinical outcomes of children before and after they transition from DGH to LAGH. Methods: Children (ages 2-13y) who were actively receiving DGH for GHD were recruited to be in a prospective studying evaluating growth, body composition, insulin resistance, adherence, quality of life, and treatment satisfaction. Participants were seen roughly every 6 months for up to 2 years. Those who chose to transition to LAGH were seen a final time 6 months after initiating LAGH. Surveys were given to participants and caregivers to evaluate adherence at each visit. Anthropometric, biochemical, and treatment data were abstracted from the electronic medical record from routine clinic visits that occurred during the study. Fasting labs, including glucose, insulin levels, and hemoglobin A1c (HbA1c) were also collected at each study visit. Results: 19 participants with GHD receiving DGH were enrolled in the study. 4 transitioned to LAGH during the time of the study. Those who switched from DGH to LAGH served as their own comparisons. There was no significant change in adherence when individuals transitioned from DGH to LAGH. Growth measures (height, weight, and BMI) were also not statistically different between children who transitioned to LAGH and those who did not. Similarly, no significant differences were observed between participants with adherence rates greater than 85% vs. those with rates below 85%. Likewise, fasting glucose, HbA1c, and insulin levels did not differ between those who transitioned to LAGH and those who did not. Conclusions: LAGH has been theorized to improve the efficacy of GHRT for patients with GHD through increasing adherence to the therapy. Such an effect was not observed as there was no change in adherence when patients switched from DGH and LAGH, nor differences in growth outcomes with increasing level of adherence. Previous reservations about LAGH have also postulated that the larger size of the LAGH molecules may limit their access to the target tissues leading to an imbalance of the linear growth and metabolic effects and that persistently elevated levels of GH from LAGH may also have a negative impact on metabolism. In patients previously on DGH, short-term LAGH use showed no evidence of altered metabolic function. Further studies are needed to better characterize the bioavailability of LAGH compared to DGH and its resulting impact on growth and metabolism over the long term.
Presentation: Saturday, July 12, 2025