Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program

Child, Christopher J.; Zimmermann, Alan G.; Chrousos, George P.; Cummings, Elizabeth A.; Deal, Cheri; Hasegawa, Tomonobu; Jia, Nan; Lawrence, Sarah; Linglart, Agnès; Loche, Sandro; Maghnie, Mohamad; Sánchez, Jacobo Pérez; Polak, Michel; Predieri, Barbara; Richter‐Unruh, Annette; Rosenfeld, Ron G.; Yeste, Diego; Yorifuji, Tohru; Blum, Werner

doi:10.1210/jc.2018-01189

Cited by 64 publications

(71 citation statements)

References 41 publications

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“…The safety profile of biosimilar rhGH treatment reported in the current interim analysis is consistent with reports from other observational studies of long-term rhGH therapy [7,9,10,[13][14][15][16][17]. Most of the AEs reported in PATRO Children were mild (54.8% of events) or moderate (27.4%) in nature.…”

Section: Discussionsupporting

confidence: 88%

“…Results from the current interim analysis indicate that Omnitrope ® is well tolerated and effective in children requiring rhGH therapy. These findings are generally consistent with those from other observational studies of pediatric rhGH treatment [7][8][9][10][11][12][13][14][15]. However, direct comparisons between the PATRO Children study and other observational registries are difficult due to differences in observational time periods and differences in safety data collection.…”

Section: Discussionsupporting

confidence: 86%

“…The incidence rate of AEs reported in the current analysis was 152.3 per 1,000 patient-years. Similar incidence rates have been reported in other observational studies that, like PATRO Children, report all AEs, regardless of causality (175.3 treatment-emergent AEs per 1,000 patient-years in the Genetics and Neuroendocrinology of Short Stature International Study; GeNeSIS [9]). The Pfizer International Growth Database (KIGS) study (which also collects all AEs) reported a slightly lower incidence rate of 96.9 AEs per 1,000 patient-years.…”

Section: Discussionsupporting

confidence: 83%

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Safety and Effectiveness of Omnitrope®, a Biosimilar Recombinant Human Growth Hormone: More Than 10 Years’ Experience from the PATRO Children Study

Pfäffle

Bidlingmaier

Kreitschmann-Andermahr

et al. 2020

Horm Res Paediatr

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Introduction: Omnitrope ® was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006. Objective: The purpose of this work was to evaluate the long-term safety and effectiveness of Omnitrope ® in PATRO Children-an ongoing, international, longitudinal, non-interventional study in children who require rhGH treatment. Methods: The study population includes infants, children, and adolescents receiving Omnitrope ®. Adverse events (AEs) are monitored for safety and rhGH effectiveness is evaluated by calculation of the height standard deviation score (HSDS), height velocity (HV), and HVSDS using height measurements and country-specific references. Results: As of November 2017, 6,009 patients from 298 centers across 14 countries were enrolled in PATRO Children. Overall, 57.7% of patients had growth hormone deficiency (GHD), 25.8% were born small for gestational age (SGA), and 4.8% had Turner syndrome (TS). In total, 84.1% were rhGH treatment naïve at study entry. The mean duration of Omnitrope ® treatment in the study was 36.1 months (range 0-133.7). Overall, 10,360 AEs were reported in 2,750 patients (45.8%). Treatment-related AEs were reported in 396 patients (6.6%; 550 events), and serious AEs (SAE) in 636 patients (10.6%; 1,191 events); 50 SAEs in 37 patients (0.6%) were considered treatment related. Following 5 years of therapy in patients who were rhGH treatment naïve at study entry, improvement from baseline in mean HSDS was +1.85 in GHD, +1.76 in SGA, and +1.0 in TS patients. In total, 912 (17.9%) patients reached adult height (n = 577 GHD, n = 236 SGA, n = 62 TS). Conclusions: This analysis of PATRO Children indicates that biosimilar rhGH is well tolerated and effective in real-world clinical practice.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 83%

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Safety and Effectiveness of Omnitrope®, a Biosimilar Recombinant Human Growth Hormone: More Than 10 Years’ Experience from the PATRO Children Study

Pfäffle

Bidlingmaier

Kreitschmann-Andermahr

et al. 2020

Horm Res Paediatr

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“…However, multiple subsequent reports did not find a consistently elevated risk of cancer incidence or mortality in GH-treated adult GHD patients [74][75][76] . Another multinational observational study from 1999-2015 on 22,311 GH-treated children from 827 investigative sites in 30 countries called GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) also did not find a significantly overall increased risk of cancer mortality or incidence [77] . On the other hand, the association between cancer risk in human patients of GH-excess/acromegaly has also been unclear.…”

Section: Gh-ghr In Cancermentioning

confidence: 93%

The effects of growth hormone on therapy resistance in cancer

Basu¹,

Kopchick²

2019

CDR

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Pituitary derived and peripherally produced growth hormone (GH) is a crucial mediator of longitudinal growth, organ development, metabolic regulation with tissue specific, sex specific, and age-dependent effects. GH and its cognate receptor (GHR) are expressed in several forms of cancer and have been validated as an anti-cancer target through a large body of in vitro, in vivo and epidemiological analyses. However, the underlying molecular mechanisms of GH action in cancer prognosis and therapeutic response had been sparse until recently. This review assimilates the critical details of GH-GHR mediated therapy resistance across different cancer types, distilling the therapeutic implications based on our current understanding of these effects.

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“…The results announced for 2015 have not yet been published but probably will confirm the known increased cardiovascular risk in patients with short stature. Recently published data from the GeNeSIS observational program, which were collected from 1999 to 2015, support the safety of pediatric growth hormone treatment [5]. However, according to the low cardiovascular risk in "otherwise healthy children" nearly all growth hormone treated children will not reach cardiovascular endpoints like myocardial infarction, sudden cardiac death or stroke in childhood.…”

Section: Introductionmentioning

confidence: 99%

Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

Buchhorn¹,

Willaschek²

2020

OJPed

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Introduction: The impact of growth hormone therapy in children with short stature on cardiovascular prognosis seems to be unpredictable from big databases. The enhanced cardiovascular risk in this group of patients may be related to adverse autonomic imprinting by early life stress. Autonomic dysfunction and possible effects of growth hormone therapy on the autonomic nervous system can be measured easily by calculating heart rate variability (HRV) from Holter electrocardiogram monitoring. Methods: We performed HRV analysis prior to growth hormone therapy (N = 33), within the first year of growth hormone therapy between 4 and 10 years of age (N = 19), at least a further HRV measurement between 10 and 15 years (N = 30). Additional measurements were performed before and after cessation of growth hormone therapy (N = 14). Data were compared to untreated pediatric patients with short stature and to age matched healthy controls. Results: Untreated patients with short stature due to growth hormone deficiency or intrauterine growth restriction in early childhood have significantly increased heart rates most of all at night and concomitantly reduced global HRV indicated as Standard Deviation of Normal to Normal Intervals (SDNN). Growth hormone treated adolescents and the untreated patients with short stature show significantly elevated mean heart rates and concomitantly reduced vagus activities measured as reduced Route Mean Square Standard Deviation (RMSSD). After cessation of growth hormone treatment SDNN significantly increases and heart rate decreases to normal values in formerly treated patients with catch-up growth. Conclusion: There is a comparable autonomic dysfunction in treated and untreated children with short stature as an indicator for enhanced cardiovascular risk.

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Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program

Cited by 64 publications

References 41 publications

Safety and Effectiveness of Omnitrope®, a Biosimilar Recombinant Human Growth Hormone: More Than 10 Years’ Experience from the PATRO Children Study

Safety and Effectiveness of Omnitrope®, a Biosimilar Recombinant Human Growth Hormone: More Than 10 Years’ Experience from the PATRO Children Study

The effects of growth hormone on therapy resistance in cancer

Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

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