Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome
Peter Bang, Joachim Woelfle, Valerie Perrot, Caroline Sert, Michel Polak, Peter Bang, Joachim Woelfle, Valerie Perrot, Caroline Sert, Michel Polak
Abstract
Objective: The European Increlex® Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex®) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS).
Design: Ongoing, open-label, observational registry (NCT00903110).
Methods: Children and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008-2017 (n = 242). The treatment-naïve/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain ≥ 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs).
Results: Height SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years' treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common.
Conclusions: In most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7849377/bin/EJE-20-0325fig1.jpg)
Figure 2
Effect of rhIGF1 therapy on…
Figure 2
Effect of rhIGF1 therapy on height SDS (A), height velocity (B), BMI SDS…
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Effect of rhIGF1 therapy on…
Figure 3
Effect of rhIGF1 therapy on height SDS (A), height velocity (B), BMI SDS…
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All targeted TEAEs for treatment-naïve/prepubertal…
Figure 4
All targeted TEAEs for treatment-naïve/prepubertal (NPP) patient subgroups (A) total, (B) serious (safety…
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- STAT5b: A master regulator of key biological pathways.Smith MR, Satter LRF, Vargas-Hernández A. Smith MR, et al. Front Immunol. 2023 Jan 23;13:1025373. doi: 10.3389/fimmu.2022.1025373. eCollection 2022. Front Immunol. 2023. PMID: 36755813 Free PMC article. Review.
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- Pubertal Timing and Growth Dynamics in Children With Severe Primary IGF-1 Deficiency: Results From the European Increlex® Growth Forum Database Registry.Bang P, Polak M, Perrot V, Sert C, Shaikh H, Woelfle J. Bang P, et al. Front Endocrinol (Lausanne). 2022 Feb 18;13:812568. doi: 10.3389/fendo.2022.812568. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 35250870 Free PMC article.
- First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model.Sia KC, Gan SU, Mohd Rodhi SH, Fu ZY, Kopchick JJ, Waters MJ, Lee KO. Sia KC, et al. Gene Ther. 2022 Jun;29(6):346-356. doi: 10.1038/s41434-022-00313-w. Epub 2022 Feb 1. Gene Ther. 2022. PMID: 35105948 Free PMC article.
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- Laron Z, Pertzelan A, Mannheimer S.Genetic pituitary dwarfism with high serum concentation of growth hormone – a new inborn error of metabolism? Israel Journal of Medical Sciences 1966. 2 152–155. - PubMed
- Observational Study
- Adolescent
- Body Height
- Body Weight / drug effects
- Child
- Female
- Growth / drug effects
- Growth Disorders / drug therapy*
- Hearing Loss, Sensorineural / drug therapy*
- Humans
- Hypoglycemia / blood
- Hypoglycemia / chemically induced
- Insulin-Like Growth Factor I / deficiency*
- Insulin-Like Growth Factor I / therapeutic use*
- Laron Syndrome / drug therapy*
- Laron Syndrome / genetics
- Longitudinal Studies
- Male
- Patient Safety
- Puberty
- Recombinant Proteins / therapeutic use*
- Treatment Outcome
- Young Adult
- Recombinant Proteins
- Insulin-Like Growth Factor I
- mecasermin
- Insulin-Like Growth Factor I Deficiency
- ClinicalTrials.gov/NCT00903110
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7849377/bin/EJE-20-0325fig2.jpg)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7849377/bin/EJE-20-0325fig3.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7849377/bin/EJE-20-0325fig4.jpg)
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Source: PubMed