Background: Due to delays in diagnosis of Idiopathic Short Stature (ISS), puberty has often started when Growth Hormone (GH) is initiated.
Objective and hypotheses: To compare GH+leuprorelin (GH+L) with GH alone in patients with ISS and at Tanner puberty stage 2 or 3. We hypothesised that co-administration of GH+L for 23 years would delay puberty, prolong GH efficacy and increase adult height.
Method: A phase 3, randomised, open-label study to examine safety and efficacy of GH to be administered until adult height reached, with or without leuprorelin, in pubertal children with ISS. However, following disclosure of the SAGhE study results, the French Drug Agency requested that GH be stopped early; consequently leuprorelin was also stopped. Patients from France entered a long-term follow-up until near adult height (NAH).
Results: Of 89 randomised patients, 45 received GH+L and 43 received GH. Mean (standard deviation; SD) GH treatment duration was 28.9 (10.9; range, 1.749.2) months with GH+L and 29.9 (10.7; range, 3.151.3) months with GH. Mean (SD) exposure to leuprorelin was 20.9 (6.4; range 3.033.1) months. Mean (SD) height velocity standard deviation score (SDS) was −0.3 (0.6) with GH+L and 0.3 (0.5) with GH at 2 years when leuprorelin was stopped; at 4 years respective values were 0.7 (0.5) and −0.0 (0.6). Mean height SDS gain from baseline was 1.0 (0.6) and 0.9 (0.4) at 4 years. Mean NAH SDS was −1.8 (0.5) in the GH+L group (n=19) and −1.8 (0.8) in the GH group (N=17). Seven versus 3 patients had bone fractures during GH+L versus GH. No deaths occurred. No unexpected adverse events occurred during or after treatment.
Conclusion: Treatments were stopped early and no conclusion can be made for comparative efficacy of GH+L versus GH alone. Long-term safety follow-up revealed no new safety concerns regarding GH treatment.
10 Sep 2016 - 12 Sep 2016