Corroboration of Height Velocity Prediction Markers for rhGH With an Oral GH Secretagogue Treatment in Children With GHD

Abstract

Context Recombinant human growth hormone (rhGH) is approved for treatment of pediatric GH deficiency (PGHD), with greatest growth responses observed in those with severe GHD. Orally administered GH secretagogues (GHS) may be useful treatment in patients with moderate GHD. Distinguishing children with severe vs. moderate GHD could identify children who would be better treated with rhGH or GHS. Objectives Evaluate baseline insulin-like growth factor-I (IGF-I) and stimulated peak GH response as predictors of 12-month height velocity (HV) in children with GHD. Design Data on children with GHD were analyzed in a legacy data base (GeNeSIS data). Participants 514 naïve to rhGH-treatment, prepubertal children with idiopathic isolated GHD (IGHD) for whom stimulated GH, baseline serum IGF-I and first year HV during rhGH treatment data are available. Outcome Measures Children with severe or moderate GHD were categorized based on GH and IGF-I data and evaluated based on baseline auxologic and hormone profiles and first year growth response to rhGH. Results Cohorts of severe and moderate GHD were 81/514 (15.8%) and 433/514 (84.2%). Cohorts differed significantly with regard to indicators of GHD (e.g., baseline height standard deviation score [SDS], height SDS minus target height SDS, HV, HV SDS, and change in height SDS during rhGH treatment). Multiple regression analysis showed IGF-I and stimulated GH were significant predictors of HV independent of other known variables. Expected first year HV in moderate GHD was 8.3 cm/year. Conclusions The combination of peak GH to GH stimulation testing and baseline IGF-I concentration are predictive enrichment markers for annualized HV responses to rhGH therapy.

Diagnosis and testing for growth hormone deficiency across the ages: a global view of the accuracy, caveats, and cut-offs for diagnosis

“…Thus, the GH response to a single low-dose LUM-201 test may have additional utility in denoting children who might not respond to a clinical trial with the secretagogue and would likely have an even greater than average response to GH therapy. Previous data ( 40 ) have also indicated that PEM-negative children with GHD would grow more robustly to treatment with GH with little additional growth with LUM-201 ( 41 ). However, PEM-positive children with GHD showed a lesser growth response to GH and a greater growth response to LUM-201 than those PEM-negative children.…”

Growth Hormone Stimulation Testing: To Test or Not to Test? That Is One of the Questions

“…and Blum et al. suggest that a partially intact pituitary axis is needed for GH secretagogues to be effective ( 17 , 18 ). Individuals with “moderate” growth hormone deficiency who may respond to GH secretagogues need to be differentiated from those with “severe” growth hormone deficiency who require growth hormone therapy ( 9 ).…”

Evolution and Future of Growth Plate Therapeutics

“…A predictive enrichment marker incorporating low pretreatment IGF-I and ability to increase GH secretion in response to LUM-201 may identify children likely to both respond and not respond to LUM-201. It is estimated by some that about 60% of children with GHD will respond to this GH secretagogue with improved GH secretion [99, 100] and increased HV [99]. A phase 2 clinical trial of LUM-201 is comparing growth rates during treatment with different doses of LUM-201 to daily hGH over 6 months in children with GHD.…”