Effects of recombinant human growth hormone treatment on growth, body composition, and safety in infants or toddlers with Prader-Willi syndrome: a randomized, active-controlled trial

Abstract

Background Prader-Willi syndrome (PWS) is a rare complex genetic disorder and is characterized by short stature, muscular hypotonia, abnormal body composition, psychomotor retardation, and hyperphagia. Recombinant human growth hormone (rhGH) treatment improves the symptoms in children with PWS, and early treatment results in more favorable outcomes. However, systematic studies in infants and toddlers under 2 years of age are lacking. This multicenter, randomized, active-controlled, parallel-group, open-label, Phase III study aimed to evaluate the safety of rhGH (Eutropin, LG Chem, Ltd.) and its efficacy on growth, body composition, and motor and cognitive development in infants and toddlers with PWS compared with a comparator treatment (Genotropin, Pfizer, Inc.). Eligible Korean infants or toddlers with PWS were randomly assigned to receive Eutropin or comparator (both 0.24 mg/kg/week, 6 times/week) for 1 year. Height standard deviation score (SDS), body composition, and motor and cognitive development were measured. Results Thirty-four subjects (less than 24 months old) were randomized into either the Eutropin (N = 17) group or the comparator (N = 17) group. After 52 weeks of rhGH treatment, height SDS and lean body mass increased significantly from baseline in both groups: the mean height SDS change (SD) was 0.75 (0.59) in the Eutropin group and 0.95 (0.66) in the comparator group, and the mean lean body mass change (SD) was 2377.79 (536.25) g in the Eutropin group and 2607.10 (641.36) g in the comparator group. In addition, percent body fat decreased significantly: the mean (SD) change from baseline was − 8.12% (9.86%) in the Eutropin group and − 7.48% (10.26%) in the comparator group. Motor and cognitive developments were also improved in both groups after the 1-year treatment. The incidence of adverse events was similar between the groups. Conclusions rhGH treatment for 52 weeks in infants and toddlers with PWS improved growth, body composition, and motor and cognitive development, and efficacy and safety outcomes of Eutropin were comparable to those of Genotropin. Hence, Eutropin is expected to provide safe and clinically meaningful improvements in pediatric patients with PWS. Trial registration The study was registered at ClinicalTrials.gov (identifier: NCT02204163) on July 30, 2014. URL: https://clinicaltrials.gov/ct2/show/NCT02204163?term=NCT02204163&rank=1

Variability and change over time of weight and BMI among adolescents and adults with Prader-Willi syndrome: a 6-month text-based observational study

“…Recombinant growth hormone (GH) therapy was approved for children with PWS in the United States in 2000 [13], and remains the only approved medication for PWS. GH is effective in normalizing growth and improving body composition in PWS, with additional positive effects on cognition and adaptive behavior, but has no effect on hyperphagia [14][15][16][17]. To date, no Food and Drug Administration (FDA)-approved drugs have proven effective in controlling appetite and food-related behavior in PWS, however, several medications are currently undergoing evaluation in clinical trials to assess impact on hyperphagia in PWS [14].…”

A retrospective analysis of growth hormone therapy in children with Schaaf–Yang syndrome

“…19 Adverse events reported during rhGH therapy in PWS include worsening of sleep apnea, respiratory tract infections and peripheral oedema. 15,20,21 rhGH therapy is contraindicated in patients with PWS who are "severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment." 22 The strong positive effect of rhGH therapy in individuals with PWS poses the question whether rhGH therapy may be a suitable treatment for individuals with SYS.…”

Early Screening and Risk Factors of Autism Spectrum Disorder in a Large Cohort of Chinese Patients With Prader-Willi Syndrome

“…Interventions that lead to increased height in PWS may substantially reduce ALP expression later in life and improve long-term prognosis. Growth hormone (GH) replacement was found not only to increase height, but also to decrease body fat and improve cognition, motor, and mental function, which is currently considered the most effective treatment for PWS (36)(37)(38)(39).…”