ESPE Abstracts (2016) 86 RFC6.7

ESPE2016 Rapid Free Communications Syndromes: Mechanisms and Management (7 abstracts)

Characteristics of Responders and Poor-responders to Increlex® Therapy – Data from Children Enrolled in the European Increlex® Growth Forum Database (EU-IGFD)

Peter Bang a , Michel Polak b , Joachim Woelfle c , Valerie Perrot d & Caroline Sert d


aDepartment of Clinical and Experimental Medicine, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden; bPaediatric Endocrinology, Gynaecology and Diabetology, Centre de référence des maladies endocriniennes rares de la croissance, Hôpital Universitaire Necker Enfants Malades, AP-HP, Université Paris Des, Paris, France; cPaediatric Endocrinology Division, Children’s Hospital, University of Bonn, Bonn, Germany; dIpsen, Boulogne-Billancourt, France


Background: The post-authorization registry, EU-IGFD, was initiated in Dec-2008 to collect data in children with growth failure receiving Increlex® (Mecasermin [rDNA Origin] Injection).

Objective and hypotheses: To report patient characteristics, safety and effectiveness data in poor-responders (i.e. with change in year 1 Height SDS <0.3).

Method: European, multicentre, open-label, observational study; eCRF data collection.

Results: As of 06-Oct-2015, 221 patients were enrolled in 10 countries, among them 93 naïve prepubertal patients (NPP) with available data including 38 poor-responders and 55 responders. In NPP, at treatment initiation poor-responders were statistically older compared to responders (multivariate analysis: OR [95% CI] =0.78 [0.69;0.90]; P<0.001). Neither gender, mid-parental adult height, height SDS, weight SDS, IGF-I nor Laron-syndrome were statistically different between groups. Median [95% CI] treatment duration in poor-responders was 1221 [891;1422], versus 1381 [1167;1829] days in responders; median dose (μg/kg BID) was 40 at treatment initiation in both subgroups, 107 versus 120 at Year 1, 120 at Year 2 in both subgroups. Baseline characteristics and effectiveness data (mean (SD)) were as follows. In the 93 NPP, the treatment-emergent adverse events (TEAEs) were 47% and 55% in poor-responders and responders, respectively, and the targeted adverse events (TAEs) were 37% and 45%. The most common TAEs in poor-responders were: hypoglycaemia (16% vs 20%), headache (13% vs 11%), tonsillar hypertrophy (11% vs 9%), and injection-site erythema (5% vs none).

Table 1. (for abstract RFC6.7)
Baseline Characteristics in NPP
Boys (%; n) Laron- Syndrome subjects (%: n) Age at first dose (years) Height SDS at first dose Weight SDS at first dose Mid-parental adult height (cm)
Poor-responders (n=38) 66; 25 8; 3 10.1 (3.9) −3.53 (1.07) −3.28 (0.94) 168.2 (9.3)
Responders (n=55) 58; 32 13; 7 7.2 (3.0) −3.68 (1.38) −3.22 (1.13) 165.7 (8.7)
Effectiveness Data in NPP
n* Height SDS Δheight SDS n* Annualized Height Velocity (cm/year) n* ΔAnnualized Height Velocity (cm/year)
Poor-responders
Baseline 38 –3.53 (1.07) 17 4.3 (2.0)
Year 1 38 –3.53 (1.12) 0.00 (0.21) 36 5.7 (1.4) 15 1.1 (2.8)
Year 2 30 –3.46 (1.24) 0.19 (0.38) 30 6.0 (1.8) 13 2.0 (3.2)
Responders
Baseline 55 –3.68 (1.38) 36 5.2 (1.6)
Year 1 55 –2.99 (1.27) 0.69 (0.30) 55 83 (1.7) 36 3.0 (2.1)
Year 2 43 –2.72 (1.29) 1.02 (0.55) 38 6.4 (1.4) 25 1.7 (1.7)
*number of available data.

Conclusion: Naïve prepubertal patients defined as poor-responders (year 1 height SDS change < 0.3) were older at the time of first Increlex intake. Other common predictors of poor response to growth promoting therapy were not identified. Poor-responders had lower second year gain in height SDS. TEAEs and TAEs were less frequent overall in poor responders. The first year Increlex response should be evaluated to determine whether to adjust treatment.

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