Growth response to an individualized versus fixed dose GH treatment in short children born small for gestational age: the OPTIMA study.

Author(s): Jung H, Land C, Nicolay C, De Schepper J, Blum WF, Schonau E

Affiliation(s): Lilly Research Laboratories, D-61352 Bad Homburg, Germany. jung_heike@lilly.com

Publication date & source: 2009-02, Eur J Endocrinol., 160(2):149-56. Epub 2008 Nov 27.

Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVE: Initial GH-induced catch up growth is highly variable in short children born small for gestational age (SGA) and mainly influenced by age at start of therapy and GH dose. This study compared the first year growth-promoting effect of an individually adjusted GH dose (IAD) versus a fixed high GH dose (FHD) in pre-pubertal children born SGA with severe short stature. DESIGN: This was a randomized, open-label, multi-center study. METHODS: The FHD group received 0.067 mg/kg per day GH throughout the 12-month study. The IAD group initially received 0.035 mg/kg per day GH; at 3 months the Cologne growth-prediction model for first year change in height SDS was applied; if predicted change was <0.75, GH was increased to 0.067 mg/kg per day for the remaining 9 months, otherwise the initial dose was continued. RESULTS: In the IAD group, 38 out of the 80 patients required the higher GH dose from month 3. From an ANCOVA for non-inferiority, mean difference in change in height SDS between IAD and FHD groups was -0.24 (95% confidence interval (CI) -0.35: -0.12), the CI for height SDS being above the pre-defined non-inferiority margin of -0.5. GH dose reductions due to IGF-I SDS >0.5 and IGFBP-3 SDS <-0.5 were performed in 4/99 FHD patients, but none of the IAD group patients. Safety data were similar between groups. CONCLUSION: With a mean treatment group difference of 1 cm in 12-month growth response, although statistically significant, the IAD group was considered non-inferior compared with the FHD group. Early growth prediction can be used to tailor the dose to the individual patient's needs, resulting in lower overall GH dose.