Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome.

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.

• Authors: Peter Bang, Joachim Woelfle, Valerie Perrot, Caroline Sert, Michel Polak
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 184 Issue 2 Pg. 267-276 (Feb 2021) ISSN: 1479-683X [Electronic] England
• PMID: 33434161 (Publication Type: Journal Article, Observational Study)

Chemical References

• Recombinant Proteins
• Insulin-Like Growth Factor I
• mecasermin

Topics

• Adolescent
• Body Height
• Body Weight (drug effects)
• Child
• Female
• Growth (drug effects)
• Growth Disorders (drug therapy)
• Hearing Loss, Sensorineural (drug therapy)
• Humans
• Hypoglycemia (blood, chemically induced)
• Insulin-Like Growth Factor I (deficiency, therapeutic use)
• Laron Syndrome (drug therapy, genetics)
• Longitudinal Studies
• Male
• Patient Safety
• Puberty
• Recombinant Proteins (therapeutic use)
• Treatment Outcome
• Young Adult