Real world data on rhIGF-1 therapy in children with severe primary IGF-I deficiency - The European experience
Jannette Saavedra1, Peter Bang2
1Instituto de Endocrinología, Metabolismo y Reproducción (IEMYR), Universidad San Francisco de Quito, Quito, Ecuador.
Insights
Recombinant human IGF-1 therapy effectively improves height in children with severe primary IGF-I deficiency (PIGFD), including Laron Syndrome. Real-world data confirms treatment benefits and identifies factors predicting response, with hypoglycemia as the main side effect.
Area of Science:
- Pediatric Endocrinology
- Growth Hormone Therapy
- Metabolic Disorders
Background:
- The Growth Hormone - Insulin-like Growth Factor axis is crucial for linear growth.
- Primary IGF-I deficiency (PIGFD) causes short stature due to GH insensitivity.
- Laron Syndrome, a severe PIGFD form, presents with extreme short stature.
Purpose of the Study:
- To review real-world data on recombinant human IGF-1 (rhIGF-1) therapy in children with severe PIGFD.
- To assess the effectiveness and safety of rhIGF-1 therapy using data from the Global IGFD registry.
- To compare treatment outcomes in SPIGFD patients with historical Laron Syndrome cohorts.
Main Methods:
- Analysis of five publications based on data from the Global IGFD registry.
- Inclusion of 346 patients with diverse PIGFD phenotypes, including Laron Syndrome.
- Assessment of short- and long-term height gain, pubertal development, and safety (hypoglycemia).
Main Results:
- rhIGF-1 therapy demonstrated significant short- and long-term height improvements in a majority of SPIGFD children.
- Height improvements were comparable to those observed in children with Laron Syndrome.
- Age at treatment initiation and baseline characteristics predict therapy response.
- Hypoglycemia is the most frequent adverse event, with increased risk in certain patient subgroups.
Conclusions:
- Real-world data from the Global IGFD registry supports the efficacy of rhIGF-1 for children with severe PIGFD.
- Treatment outcomes are consistent with previous findings and comparable across different PIGFD phenotypes.
- Further analysis of registry data can refine treatment strategies and identify predictive factors for optimal growth response.
Abstract:
The Growth Hormone - Insulin-like Growh Factor - axis promotes linear growth in children and adolescents and accounts for approximately 1/3 of adult height. In Primary IGF-I deficiency (PIGFD) insensitivity to the actions of GH results in short stature. The most severe phenotype in children with genetic defects in the GH receptor gene is known as Laron Syndrome with height SDS of -6 to -12 in childhood and an adult height of 120-130 cm. Treatment with recombinant human (rh) IGF-1 is approved to promote linear growth in children with severe PIGFD and the EMA approval required that data on children on therapy and up to 5 years post-treatment is collected in the Global Increlex Growth Forum Database (IGFD) registry. In this review, the findings in five publications on rhIGF-1 therapy in children with SPIGFD based on data from the Global IGFD registry are discussed and compared with previous publications on cohorts of patients with severe PIGFD including children with Laron Syndrome. The registry started inclusion of patients in 2008 from 10 European countries (EU IGFD Registry) and have continued collecting data from eight European countries and the US since 2021 (Global IGFD registry). At data cut-off (03 April 2025), there were 346 patients in the registry database including patients with a large variation of phenotypes from Laron Syndrome to a less severe phenotype. The findings include real-world data on effectiveness assessing short- and long-term height gain as well as near adult height, pubertal development and growth dynamics and safety assessing hypoglycemic events, which is the most frequent targeted adverse event. Real-world data from the Global IGFD registry confirms previous data on rhIGF-1 therapy and demonstrates that short and long-term height improves in a majority of children with SPIGFD with similar height improvements compared to children with Laron Syndrome. The registry data points to baseline characteristics including age at treatment initiation that predicts response to therapy. Hypoglycemia is the most common adverse event and hypoglycemia prior to start of therapy or a diagnosis of Laron Syndrome increases the risk. However, very few events over a course of therapy are reported on an individual basis.
