Long-Term Safety of Recombinant Human Growth Hormone in Children

Bell, Jennifer J.; Parker, Katrina; Swinford, Rita D.; Hoffman, Andrew R.; Maneatis, Thomas; Lippe, Barbara M.

doi:10.1210/jc.2009-0178

Cited by 265 publications

(230 citation statements)

References 45 publications

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“…The safety profile of GH treatment reported in our study is consistent with findings from other observational studies (11,29,33,34). Furthermore, our data collected from a large, multinational, observational study demonstrate no association between GH dose up to the event and the occurrence of ADRs in patients with short stature across various indications.…”

Section: Discussionsupporting

confidence: 91%

“…Comparision of the IRs for AEs reported in NordiNet ® IOS with those reported in other GH observational studies can be seen in Table 3 (11,26,26,27,28,29,30,31,32). With the exception of SAEs in the intermediaterisk group, the IR for all AEs was independent of GH dose ( Figs 1B and 2B).…”

Section: European Journal Of Endocrinologymentioning

confidence: 65%

“…The lower IRs for AEs reported in our study compared with other observational studies may be a consequence of the differences in study time periods (38) as well as differences in the types of AEs reported in each study. Differences in the types of events reported may at least partly explain the higher IRs for AEs reported in KIGS (103.1 events per 100 000 patient-years of exposure) (31) compared with NCGS (20.9 events per 100 000 patient-years of exposure) (11). In particular, it was mandatory to report all AEs in the KIGS registry; by contrast, only adverse clinical or laboratory findings suspected to be related to GH treatment, irrespective of causality, were required to be reported in NCGS (39).…”

Section: Discussionmentioning

confidence: 99%

“…Theoretical concerns of a link between excess GH and increased morbidity in patients with acromegaly (4,5) resulted in the initiation of several state-regulated, mandatory, registries of GH-treated patients in Europe as well as post-approval surveillance studies, which were established, managed, and supported by manufacturers of GH in Europe and the USA (6,7,8,9). Accumulated experience of GH treatment captured in these large observational databases supports a favorable safety profile (10,11). However, in 2012, preliminary data from the French cohort of the Safety and Appropriateness of Growth Hormone Treatments in Europe (SAGhE) study, a retrospective evaluation of 6928 patients diagnosed with GHD, ISS, or born SGA and treated as children with GH, raised concerns regarding the long-term safety of GH therapy and suggested a link between GH use during childhood and premature death (12).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Is safety of childhood growth hormone therapy related to dose? Data from a large observational study

Sävendahl

Pournara

Pedersen

et al. 2016

European Journal of Endocrinology

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Section: Discussionsupporting

confidence: 91%

Section: European Journal Of Endocrinologymentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is safety of childhood growth hormone therapy related to dose? Data from a large observational study

Sävendahl

Pournara

Pedersen

et al. 2016

European Journal of Endocrinology

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“…Based on the fact that the growth response in the first year is associated with the long-term outcome, it is reasonable to evaluate the growth response as early as possible to predict the long-term outcome [28][29][30]. Although the experience with GH therapy over 30 years suggests that GH treatment is safe [31,32], discussions about adverse effects especially in the long-term flared up again recently because of results from the French cohort of the Safety and Appropriateness of Growth Hormone Treatments in Europe (SAGhE) study [33,34]. Moreover, treatment costs are very high.…”

Section: Discussionmentioning

confidence: 99%

Growth response to growth hormone treatment in patients with SHOX deficiency can be predicted by the Cologne prediction model

Hoyer‐Kuhn

Franklin

Jones

et al. 2017

Journal of Pediatric Endocrinology and Metabolism

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Background: Growth hormone (GH) treatment in children with short stature homeobox-containing gene (SHOX) deficiency is recognized to increase height velocity (HV) and adult height. Prediction of growth response continues to be a challenge. A comparatively accurate method is the Cologne prediction model developed in children with GH deficiency. The aim was to investigate whether this model also applies to patients with SHOX deficiency. Methods: Included were 48 patients with SHOX deficiency confirmed by DNA analysis and treated with 0.05 mg/kg/ day of somatropin. Prediction by the Cologne model uses the following variables: relative bone age (BA) retardation, baseline insulin-like growth factor-I (IGF-I), urinary deoxypyridinoline (DPD) cross-links at 4 weeks and HV at 3 months. Results: HV and height standard deviation scores (SDS) increased significantly during the first year of treatment. Predicted and observed HV (cm/year) showed a Pearson correlation coefficient of 0.50 (p < 0.001; root-meansquare error = 1.63) and for first-year change in height SDS a Pearson correlation coefficient of 0.751 (p < 0.001; root-mean-square error = 0.32). Poor response could be adequately predicted using SDS change, with sensitivity and specificity both above 70% for certain thresholds. Conclusions:The results demonstrate that the Cologne model can be used to predict growth response in patients

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Association of Childhood Growth Hormone Treatment With Long-term Cardiovascular Morbidity

et al. 2021

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IMPORTANCE Concerns about the cardiovascular safety of recombinant human growth hormone (rhGH) treatment in childhood have recently been raised; however, long-term studies are limited.OBJECTIVE To investigate the long-term risk of overall and severe cardiovascular events in patients previously treated with rhGH in childhood and whether there is an association with treatment duration or dose. DESIGN, SETTING, AND PARTICIPANTSThis nationwide population-based cohort study included patients treated with rhGH during childhood from January 1, 1985, to December 31, 2010, in Sweden, with follow-up through December 31, 2014. Included patients were treated with rhGH owing to isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS). For each patient, 15 age-, sex-, and region-based matched control individuals were randomly selected from the general population as a comparison group. Data on cardiovascular outcomes and covariates including gestational age, birth weight, birth length, socioeconomic status, and height were obtained through linkage with several health care and population-based registers. Data were analyzed from January 1, 1985, to December 31, 2014.EXPOSURES Treatment with rhGH during childhood and adolescence (aged 0-18 years). MAIN OUTCOMES AND MEASURESThe primary outcome was the first cardiovascular event recorded after the start of follow-up, and the secondary outcome was the first severe cardiovascular event.RESULTS A total of 53 444 individuals (3408 patients and 50 036 controls; 67.7% men; mean [SD] age at study end, 25.1 [8.2] years) were followed up for as long as 25 years (median follow-up, 14.9 [range, 0-25] years; total, 795 125 person-years). Among 1809 recorded cardiovascular events, the crude incidence rates were 25.6 events per 10 000 person-years for patients and 22.6 events per 10 000 person-years for controls. The adjusted hazard ratio (HR) for all cardiovascular events was higher in patients compared with controls (HR, 1.69; 95% CI, 1.30-2.19), especially for women (HR, 2.05; 95% CI, 1.31-3.20) compared with men (HR, 1.55; 95% CI, 1.12-2.13). All subgroups had increased HRs (SGA, 1.97 [95% CI,; GHD, 1.66 [95% CI, and ISS, 1.55 [95% CI,). Longer duration of rhGH treatment (HR, 2.08; 95% CI,) and total cumulative dose (HR, 2.05; 95% CI, 1.18-3.55) were associated with higher risk for overall cardiovascular disease. The adjusted HR for severe cardiovascular disease was 2.27 (95% CI, 1.01-5.12). CONCLUSIONS AND RELEVANCEIn this cohort study, treatment with rhGH during childhood due to GHD, SGA, or ISS was associated with increased risks of cardiovascular events in early adulthood, particularly in women; however, conclusions of causality are still limited and the absolute risk remains low.

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Long-Term Safety of Recombinant Human Growth Hormone in Children

Cited by 265 publications

References 45 publications

Is safety of childhood growth hormone therapy related to dose? Data from a large observational study

Is safety of childhood growth hormone therapy related to dose? Data from a large observational study

Growth response to growth hormone treatment in patients with SHOX deficiency can be predicted by the Cologne prediction model

Association of Childhood Growth Hormone Treatment With Long-term Cardiovascular Morbidity

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