Treatment of Children With GH in the United States and Europe: Long-Term Follow-Up From NordiNet® IOS and ANSWER Program

Sävendahl, Lars; Polak, Michel; Backeljauw, Philippe; Blair, Jo; Miller, Bradley S.; Rohrer, Tilman; Pietropoli, Alberto; Ostrow, Vlady; Ross, Judith L.

doi:10.1210/jc.2019-00775

Cited by 40 publications

(43 citation statements)

References 29 publications

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“…Patient data from the ANSWER Program® were obtained over a 14-year period (June 24, 2002 to September 30, 2016) from 207 participating sites within the United States, while data from NordiNet® IOS were collected over 10 years (April 1, 2006 to December 31, 2016) from 469 clinics in 22 countries in Europe and the Middle East. The ANSWER Program® and NordiNet® IOS originally enrolled 20,204 and 17,995 pediatric patients, respectively [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…The doses of GH administered to participants were selected by treating physicians, and data on parameters such as baseline height standard deviation score (HSDS), weight, bone age, maximal stimulated serum GH concentration, serum insulin-like growth factor 1 (IGF-1) levels, and GH dose/frequency were collected [17]. Patient data from the ANSWER Program® were obtained over a 14-year [20].…”

Section: Data Sourcementioning

confidence: 99%

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Outcomes in children treated with growth hormone for Prader-Willi syndrome: data from the ANSWER Program® and NordiNet® International Outcome Study

Angulo

Abuzzahab

Pietropoli

et al. 2020

Int J Pediatr Endocrinol

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Background Growth hormone (GH) deficiency is common in patients with Prader-Willi syndrome (PWS) and leads to short adult stature. The current study assessed clinical outcomes based on real-world observational data in pediatric patients with PWS who were treated with GH. Methods Data from patients previously naïve to treatment with GH who began therapy with somatropin were collected from 2006 to 2016 in the observational American Norditropin® Studies: Web-Enabled Research (ANSWER) Program® and NordiNet® International Outcome Study. Variables affecting change from baseline in height standard deviation scores (HSDS; n = 129) and body mass index standard deviation scores (BMI SDS; n = 98) were determined. Results Patients included in both HSDS and BMI SDS analyses were treated with a mean GH dose of 0.03 mg/kg/d (SD, 0.01 mg/kg/d). Results from the HSDS analysis revealed that baseline age and years on treatment had a significant impact on the change in HSDS. In the BMI SDS analysis, longer GH treatment time led to a greater change in BMI SDS from baseline, and patients with a higher BMI at the start of treatment had a greater decrease in BMI over time. Conclusions GH is effective in the management of children with PWS. Earlier treatment resulted in a greater gain in height, and a longer treatment period resulted in better outcomes for both height and BMI. Trial registration This study was registered with ClinicalTrials.gov (NCT01009905) on November 9, 2009.

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Section: Methodsmentioning

confidence: 99%

Section: Data Sourcementioning

confidence: 99%

Outcomes in children treated with growth hormone for Prader-Willi syndrome: data from the ANSWER Program® and NordiNet® International Outcome Study

Angulo

Abuzzahab

Pietropoli

et al. 2020

Int J Pediatr Endocrinol

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“…The ANSWER study collected patient data over a 14-year period (24 June 2002 to 30 September 2016), originally from 207 participating sites within the United States, of which 144 remained active by the end of the study. Of an initial 20,204 pediatric patients enrolled in ANSWER, 12,660 patients contributed to effectiveness outcomes assessments (GHD n = 8580; ISS n = 2367; other conditions n = 1713) [21].…”

Section: Data Sourcementioning

confidence: 99%

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

Ross

Ostrow

2020

Int J Pediatr Endocrinol

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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

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“…The FDA approval for GH therapy of ISS consolidated this category of patients in the minds of paediatricians with data on efficacy and safety accumulating in international databases such as the Kabi international growth study (KIGS) and NCGS ( 33 ). Results of cohorts of ISS subjects were, and still are, being regularly analysed and published ( 34 , 35 ), and are used as the basis for management guidelines ( 5 , 36 ). ISS is also used as a diagnostic category in the International Classification of Pediatric Endocrine Disorders ( www.icped.org ) ( 6 ).…”

Section: Idiopathic Short Staturementioning

confidence: 99%

Growth failure: ‘idiopathic’ only after a detailed diagnostic evaluation

Rapaport

Wit

Savage

2021

Endocrine Connections

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The terms idiopathic short stature (ISS) and small for gestational age (SGA) were first used in the 1970s and 1980s. ISS described non-syndromic short children with undefined aetiology who did not have growth hormone (GH) deficiency, chromosomal defects, chronic illness, dysmorphic features or low birth weight. Despite originating in the pre-molecular era, ISS is still used as a diagnostic label today. The term SGA was adopted by paediatric endocrinologists to describe children born with low birth weight and/or length, some of whom may experience lack of catch-up growth and present with short stature. GH treatment was approved by the FDA for short children born SGA in 2001, and by the EMA in 2003, and for the treatment of ISS in the US, but not Europe, in 2003. These approvals strengthened the terms SGA and ISS as clinical entities. While clinical and hormonal diagnostic techniques remain important, it is the emergence of genetic investigations that have led to numerous molecular discoveries in both ISS and SGA subjects. The primary message of this article is that the labels ISS and SGA are not definitive diagnoses. We propose that the three disciplines of clinical evaluation, hormonal investigation and genetic sequencing should have equal status in the hierarchy of short stature assessments and should complement each other to identify the true pathogenesis in poorly growing patients.

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Treatment of Children With GH in the United States and Europe: Long-Term Follow-Up From NordiNet® IOS and ANSWER Program

Cited by 40 publications

References 29 publications

Outcomes in children treated with growth hormone for Prader-Willi syndrome: data from the ANSWER Program® and NordiNet® International Outcome Study

Outcomes in children treated with growth hormone for Prader-Willi syndrome: data from the ANSWER Program® and NordiNet® International Outcome Study

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

Growth failure: ‘idiopathic’ only after a detailed diagnostic evaluation

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