Ten Years After the United States Food and Drug Administration (US FDA) Approval of GH Treatment for Children with Idiopathic Short Stature (ISS): Who is Being Treated and What is the Response to Treatment?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 624-646-Growth: Clinical Trials & Observational Studies
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-632
Charmian A Quigley*1, Christopher J Child2, Alan G Zimmermann3, Judith L Ross4, Ron G Rosenfeld5 and Werner F. Blum6
1Lilly Research Laboratories, Indianapolis, IN, 2Eli Lilly and Company, Windlesham, United Kingdom, 3Eli Lilly and Company, Indianapolis, IN, 4Thomas Jefferson University, Philadelphia, PA, 5Stat 5 LLC, Los Altos, CA, 6Eli Lilly and Company, Bad Homburg, Germany
Background: The controversial 2003 US FDA approval of GH treatment for children with ISS raised concerns of potential for inappropriate GH use. 

Objective: To compare clinical characteristics of GH-treated US children with ISS followed in a prospective observational study to those with GH deficiency (GHD) at baseline and during GH treatment.

Patients/Methods: From ~8,000 children (all diagnoses combined) followed in the USA in GeNeSIS* we compared data for 1636 patients with investigator-provided diagnoses of ISS (n=711) or GHD (n=925) who were naïve to GH at baseline and had follow-up data at ≥2 yr of treatment.

Results: As a proportion of total patients with enrollment diagnoses of ISS or GHD, the percent with ISS increased from 14% in 2002 (year pre-approval) to 43% in 2004 (year post-approval) and was 35% overall.  Patients with ISS (77% Caucasian; 73% male) were clinically similar to those with GHD (80% Caucasian; 75% male), but were significantly older, shorter, thinner, had shorter parents, and, not surprisingly, higher IGF-I and peak stimulated GH values. Mean±SD baseline values for ISS vs GHD groups were: age 11.4±2.9 vs 10.7±3.7 yr; bone age 10.3±2.9 vs 9.5±3.4 yr; height standard deviation score (SDS) -2.34±0.73 vs -2.16±0.97; height velocity SDS -0.83±1.51 vs -0.98±1.87; mid-parental (target) height SDS -0.48±0.76 vs -0.26±0.87; body mass index (BMI) SDS -0.61±1.40 vs -0.25±1.68; peak GH (µg/L) median [Q1, Q3]: ISS, 14.5 [11.4, 19.8] vs GHD, 6.9 [4.4, 9.5].

Although there were significant differences between groups at baseline, responses to GH treatment were similar, with both groups demonstrating catch-up growth, though of slightly lower magnitude for ISS vs GHD in both 1st and 2nd yr, despite a slightly higher GH dose (0.33±0.07 vs 0.31±0.08 mg/kg/wk). 1st-yr response: attained height SDS -1.80±0.73 vs -1.54±0.93; height SDS gain 0.54±0.32 vs 0.62±0.49; height velocity SDS 2.44±2.00 vs 2.61±2.14; BMI SDS -0.35±1.19 vs -0.05±1.49; 2nd-yr response: attained height SDS -1.48±0.77 vs -1.16±1.00; height SDS gain 0.34±0.33 vs 0.40±0.39; height velocity SDS 1.56±1.77 vs 1.80±2.09; BMI SDS -0.11±1.20 vs 0.15±1.48. For the subset of patients with data available, 4th-yr attained height SDS and height SDS gain (respectively) were -1.10±0.84 and 0.15±0.34 for ISS (n=234) vs -0.70±1.07 and 0.20±0.31 for GHD (n=328).

Safety of GH treatment appeared similar, with overall treatment discontinuations due to adverse events of 1.1% for GHD vs 0.6% for ISS. 

Conclusions: Enrollment of children with ISS in GeNeSIS increased substantially following the 2003 FDA approval of the indication, but patients with ISS are on average somewhat shorter and older than those with GHD, and respond similarly, though somewhat less well, to treatment.  These findings suggest that US pediatric endocrinologists select children for GH treatment primarily on the basis of clinical rather than biochemical parameters.

Disclosure: CAQ: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. CJC: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. AGZ: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. JLR: Research Funding, Novo Nordisk, Research Funding, Eli Lilly & Company, Consultant, Novo Nordisk, Consultant, Eli Lilly & Company, Consultant, Abbott Laboratories, Research Funding, Pfizer, Inc.. RGR: Medical Advisory Board Member, Eli Lilly & Company. WFB: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: *Data from the Genetics and Neuroendocrinolgy of Short Stature International Study (GeNeSIS), sponsored by Eli Lilly and Company