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.

Figures

Figure 1

Study disposition and patient subgroup distribution. Responders were defined as patients with a change in height SDS in year 1 of ≥0.3; poor-responders were defined as patients with a change in height SDS in year 1 of

Figure 2

Effect of rhIGF1 therapy on height SDS (A), height velocity (B), BMI SDS (C), and weight SDS (D) in treatment-naïve/prepubertal (NPP) patients with or without LS (registry population). Data are mean (s.d.). n, number of patients with available data at each time point; LS, Laron syndrome; SDS, standard deviation score.

Figure 3

Effect of rhIGF1 therapy on height SDS (A), height velocity (B), BMI SDS (C), and weight SDS (D) in treatment-naïve/prepubertal (NPP) responders and poor-responders without LS (registry population). Data are mean (s.d.). Responders were defined as patients with a change in height SDS in year 1 of ≥ 0.3. Poor-responders were defined as patients with a change in height SDS in year 1 of < 0.3. n, number of patients with available data at each time point. LS, Laron syndrome; non-NPP, not treatment naïve and/or pubertal; SDS, standard deviation score.

Figure 4

All targeted TEAEs for treatment-naïve/prepubertal (NPP) patient subgroups (A) total, (B) serious (safety population). All reported targeted TEAEs and serious targeted TEAEs are shown. Targeted TEAEs were: headache, chronic middle ear infection, papilledema, hypoglycaemia, acromegalic facial changes, oedema, gynaecomastia, hearing loss, intracranial hypertension, lipohypertrophy at injection sites, myalgia, sleep apnoea, tonsillar hypertrophy and cardiomegaly. Hearing impairment was coded as deafness. Responders were defined as patients with a change in height SDS in year 1 of ≥0.3. Poor-responders were defined as patients with a change in height SDS in year 1 of