First line treatment evaluation in patients with severe primary insulin-like growth factor 1 deficiency (SPIGFD): Data from the Global Increlex<sup>®</sup> Registry

Peter Bang; Philippe Backeljauw; Joachim Woelfe; Artur Bossowski; Iwona Beń-Skowronek; Jesús Argente; Schepper Jean De; Valérie Perrot; Caroline Sert; Mohamad Maghnie

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ESPE Abstracts (2024) 98 FC5.6

ESPE2024 Free Communications Growth and Syndromes (6 abstracts)

First line treatment evaluation in patients with severe primary insulin-like growth factor 1 deficiency (SPIGFD): Data from the Global Increlex^® Registry

Peter Bang ¹ , Philippe Backeljauw ² , Joachim Woelfe ³ , Artur Bossowski ⁴ , Iwona Beń-Skowronek ⁵ , Jesús Argente ⁶ , Jean De Schepper ^7,8 , Valérie Perrot ⁹ , Caroline Sert ⁹ & Mohamad Maghnie ^10,11,8

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¹Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden. ²Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. ³Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany. ⁴Department of Paediatrics, Endocrinology, and Diabetology with Cardiology Division, Medical University of Bialystok, Bialystok, Poland. ⁵Department of Paediatric Endocrinology and Diabetology with Laboratory of Endocrinology and Metabolism, Medical University of Lublin, Lublin, Poland. ⁶Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de la Fisiopatología (CIBER) de Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III and IMDEA Food Institute, Madrid, Spain. ⁷Department of Pediatrics, UZ Brussels, Free University of Brussels, Brussels, Belgium. ⁸Endo-ERN European Reference Network on Rare Endocrine Conditions, Amsterdam, Netherlands. ⁹Ipsen, Boulogne-Billancourt, France. ¹⁰Department of Pediatrics, IRCCS Istituto Giannina Gaslini, University of Genova, Genova, Italy. ¹¹Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy

Background: Severe primary insulin-like growth factor-1 deficiency (SPIGFD) is a rare growth disorder characterised by extreme short stature, low serum IGF-1 and normal/elevated serum growth hormone (GH). Some patients receive GH treatment before recombinant human IGF-1 (rhIGF-1; Increlex^® [mecasermin]). We investigated rhIGF-1 effectiveness and tolerability in patients previously treated with GH versus GH naïve patients at rhIGF-1 initiation.

Methods: Descriptive analyses of rhIGF-1 treatment in prepubertal patients with SPIGFD in the Global Increlex^® Registry (NCT00903110), with and without previous GH treatment. Linear regression analyses (unadjusted and adjusted by inverse probability of treatment weighting) compared height standard deviation score change from baseline (ΔHtSDS) at Year 1 between the populations.

Results: At data cut-off (20 April 2023), 174 GH-naïve and 41 patients with previous GH treatment were enrolled. At baseline, GH-naïve patients were younger, had greater HtSDS, lower height velocity and lower serum IGF 1 than patients with previous GH treatment (Table). ΔHtSDS was greater in patients who were GH-naïve versus those with previous GH treatment at Year 1 (P = 0.038 when adjusted for baseline parameters; Table). Similar proportions of patients presented ≥1 treatment emergent adverse events (TEAEs); 61.0% (n = 25/41) previously treated versus 65.9% (n = 114/173) GH-naïve. Hypoglycaemia was the most frequent TEAE in both groups.

Table. Baseline characteristics/effectiveness
		Previous GH treatment (n = 41)	GH-naïve (n = 174)
Age, years	Mean (SD) 95%CI	9.5 (3.4) 8.4;10.5	7.8 (3.7) 7.2;8.3
HtSDS	n Mean (SD) 95%CI	39 −3.5 (1.3) −3.9;−3.1	157 −3.8 (1.5) −4.0;−3.6
Height velocity, cm/year		30 5.2 (1.9) 4.5;6.0	86 4.7 (1.7) 4.3;5.1
BMI SDS		37 −1.2 (1.2) −1.6;−0.8	142 −0.8 (1.3) −1.1;−0.6
IGF-1 levels, ng/mL		38 111.7 (126.3) 70.2;153.2	161 69.8 (61.7) 60.2;79.4
Year 1 ΔHtSDS		Previous GH treatment (n = 35)	GH-naïve (n = 128)	Estimated difference (95%CI) p-value
Raw data	Mean (SD) 95%CI	0.25 (0.51) 0.08;0.43	0.40 (0.43) 0.33;0.48	-
Unadjusted comparison^a	Adjusted mean (SD)	0.27 (0.07)	0.40 (0.04)	0.12 (−0.04;0.29) 0.141
Adjusted comparison^a,b		0.28 (0.04)	0.41 (0.04)	0.13 (0.01;0.25) 0.038
^aLinear regression analysis including baseline HtSDS and patient group as covariates; ^bModel based on inverse probability of treatment weighting method, propensity score computed with baseline characteristics: sex, age, HtSDS, height velocity, BMI SDS, IGF-1 level and highest stimulated GH level.

Conclusion: With rhIGF-1 treatment in SPIGFD, GH-naïve patients gained more height versus patients previously treated with GH when adjusted for baseline parameters. Our assessment did not consider height response to GH or baseline characteristics at GH initiation.