Dataset Information

Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program.

ABSTRACT: Background:Treatment of children with growth hormone deficiency (GHD) or idiopathic short stature (ISS) using GH is only effective for bone growth prior to epiphyseal fusion. Aromatase inhibitor therapy (AIT) blocks estrogen production, thereby delaying epiphyseal fusion. The current study analyzed baseline characteristics and longitudinal data of male patients with GHD or ISS who were treated with GH and concomitant AIT. Methods:Data were obtained from the observational American Norditropin® Studies: Web-Enabled Research (ANSWER) Program, which collected efficacy and safety data of patients treated with Norditropin®. A longitudinal cohort approach compared patient characteristics, including chronologic age, bone age, and height standard deviation score (HSDS), in GH-treated males before and after AIT initiation. Results:A total of 142 GH-naïve patients with GHD (n?=?115) or ISS (n?=?27) with mean (± SD) baseline chronological ages of 12.10?±?3.00 and 10.76?±?3.07?years, respectively, were analyzed. The majority were classified at advanced Tanner stages II to V. Patients with GHD had mean HSDS of -?1.97?±?0.78 at baseline and?-?0.99?±?0.88 prior to AIT initiation, while corresponding values for patients with ISS were?-?2.15?±?0.72 and?-?1.04?±?0.79, respectively. In patients evaluated after 2?years of concomitant AIT, mean HSDS had decreased to -?0.40?±?1.16 and?-?0.65?±?0.52 for patients with GHD and ISS, respectively. Patients with GHD had a mean bone age/chronological age ratio (BA/CA) of 0.91?±?0.11 at baseline and 0.97?±?0.10 prior to AIT initiation, while corresponding values for patients with ISS were 0.85?±?0.16 and 0.99?±?0.10, respectively. In patients evaluated after 2?years of concomitant AIT, mean BA/CA values were 0.95?±?0.10 and 0.96?±?0.06 for patients with GHD and ISS, respectively. Conclusions:In this real-world analysis, use of AIT with GH in males appeared to be associated with ongoing growth over 2?years, and AIT likely augmented growth potential as indicated by continued HSDS increase with decreased BA/CA after AIT initiation. Trial registration:This trial was sponsored by Novo Nordisk and is registered with ClinicalTrials.gov (NCT01009905). Registered November 11, 2009; retrospectively registered.

SUBMITTER: Miller BS

PROVIDER: S-EPMC7537098 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program.

Miller Bradley S BS Ross Judith J Ostrow Vlady V

International journal of pediatric endocrinology 20201006

<h4>Background</h4>Treatment of children with growth hormone deficiency (GHD) or idiopathic short stature (ISS) using GH is only effective for bone growth prior to epiphyseal fusion. Aromatase inhibitor therapy (AIT) blocks estrogen production, thereby delaying epiphyseal fusion. The current study analyzed baseline characteristics and longitudinal data of male patients with GHD or ISS who were treated with GH and concomitant AIT.<h4>Methods</h4>Data were obtained from the observational American ...[more]

PMID: 33042202

Similar Datasets

Project description:BackgroundChildren with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually less that 4 cm, and they remain short as adults. The benefit obtained seems dose dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of 0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has remained controversial.ObjectiveThe objective was to conduct a retrospective analysis of our experience with 123 children with ISS treated with 0.32 ± 0.03 mg/kg/week of rhGH, with the aim of comparing the different subgroups of non-familial short stature, familial short stature, normal puberty, and delayed puberty and to assess the benefit by comparison with 305 untreated historical controls, from nine different randomized and nonrandomized controlled studies.ResultsEighty eight of our children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females. In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts. This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known. The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty.ConclusionOur experience was quite positive with normalization of the heights and growth of the children during childhood and the attainment of normal adult heights, the main two aims of treatment.

Project description:BackgroundThe study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD).MethodsTotal 163 patients aged 2-18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment.ResultsThe baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment.ConclusionThe 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.Trial registrationClinicalTrials.gov Identifier: NCT01604395.

Project description:Abstract TransCon Growth Hormone in the Treatment of Pediatric Growth Hormone Deficiency: Results of the Phase 3 heiGHt TrialBackground TransCon Growth Hormone is a sustained-release recombinant human growth hormone (hGH; somatropin) prodrug in development as a long-acting GH (LAGH) for children with growth hormone deficiency (GHD). In its prodrug form, TransCon hGH is inactive with hGH transiently bound to a TransCon carrier via a TransCon linker. Upon injection and triggered by physiological pH and temperature, unmodified recombinant hGH is sustainably released and thus designed to maintain the same mode-of-action and distribution as daily hGH replacement therapy but with once-weekly dosing. In a 6-month phase 2 trial of TransCon hGH vs. a daily hGH in children with GHD, mean annualized height velocity (AHV) for TransCon hGH was 12.9 cm/y compared to 11.6 cm/y for a daily hGH at an equivalent hGH dose (0.21 mg/kg/wk). The subsequent pivotal phase 3 global heiGHt Trial (ClinicalTrials.gov: NCT02781727) was designed to investigate the safety, tolerability, and efficacy of weekly TransCon hGH versus daily hGH over 52 weeks in treatment-naive prepubertal children with GHD. Methods Subjects were randomized in a 2:1 ratio and received either once-weekly TransCon hGH 0.24 mg hGH/kg/wk or dose-equivalent once-daily Genotropin over 52 weeks. Key baseline demographics variables included age, gender, height standard deviation score (SDS), IGF-1 SDS, peak stimulated GH, and bone age delay. Study endpoints included AHV, IGF-1 response, immunogenicity, and safety. Results At baseline, the mean age of study participants, of whom 82% were male, was 8.5 years. Mean height SDS was -2.93, and mean IGF-1 SDS was -2.04. Mean peak stimulated GH was 5.77 µg/L, and mean bone delay was 2.63 years. The final sample size (n=161) was larger than planned (n=150) which strengthens the study power for noninferiority. Top-line results, including AHV, change in height SDS, serum IGF-1 levels, change in bone age, and adverse events, will be available for presentation at ENDO 2019. Conclusion Only LAGHs based on unmodified hGH have obtained approval in Europe or the United States. By February 2019, all subjects will have completed their participation in this pivotal trial of a LAGH designed to release unmodified hGH, with top-line analyses available in March. The heiGHt Trial was well-powered to demonstrate noninferiority between TransCon hGH and a daily hGH, with baseline demographic variables in the range of recent GH trials.

Dataset Information

Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program.

Publications

Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets