Combination GH, IGF-1 treatment accelerated height velocity in short children

LWPES/ESPE 8th Joint Meeting

Preliminary data suggest that combination treatment with recombinant human growth hormone and insulin-like growth factor-1 may be associated with robust catch-up growth in prepubertal children of short stature with low IGF-1 and normal GH.

Researchers conducted an ongoing randomized study based on the hypothesis that combination treatment may outperform both monotherapies. The study included 106 treatment-naive prepubertal children with height SDS <–2, IGF-1 SDS <–1, and stimulated GH ≥10 ng/mL.

Children were randomly assigned to once-daily morning injections of rhGH 45 mcg/kg or combination injections of rhGH plus three doses of IGF-1 (50 mcg/kg, 100 mcg/kg or 150 mcg/kg).

The researchers presented efficacy data on 36 children enrolled in the efficacy analysis as of August 2009. First-year height velocity — the primary endpoint — was greatest among children assigned to rhGH plus IGF-1 150 mcg/kg (12.1 cm per year). Children assigned to rhGH monotherapy experienced a 9.2-cm per year increase compared with 10.4 cm per year with rhGH plus IGF-1 50 mcg/kg and 10.7 cm per year with rhGH plus IGF-1 100 mcg/kg.

First-year change in height was again greater in the high dose combination group (1.11 SDS) and lowest with rhGH monotherapy (0.72 SDS).

Seven children had dose reductions because of IGF-1 scores above 4; all were in the higher dose combination groups.

“At this point, tracking data will lead us to believe there will be some substantial increases in first-year height velocity,” George Bright, MD, vice president and medical director of endocrinology at Tercica, a subsidiary of Ipsen, said during the session. Further, changes in height age related to bone age were favorable, he added.

Based on safety data, the most common adverse event was headache. Four serious adverse events were reported in two children assigned to combination therapy, including transient papilledema; patients stopped and restarted therapy without recurrence.

“Preliminary results for [combination treatment] suggest that annualized height velocity is accelerated in short children with non-severe primary IGF-1 deficiency. This treatment should remain a research endeavor until adequate efficacy and safety data are compiled and evaluated,” the researchers concluded.

The study represents investigational use of combination of GH and IGF-1, and such use is not approved by the FDA, according to the researchers.

This is an ongoing, three-year study. – by Katie Kalvaitis

For more information:

Midyet LK. #FC-10-006. Presented at: LWPES/ESPE 8th Joint Meeting; September 9-12, 2009; New York.

The study researchers basically tried a whole new therapeutic approach and these results are very exciting. Understand that these are preliminary data — one year — and we need to see that the results were sustained and the safety profile remains good. We have known that the long-term results associated with GH and IGF-1 are good; these are important building blocks. Now, we have data on the two together that have never before been confirmed.

– Ron G. Rosenfeld, MD

Professor of Cell and Developmental Biology, Oregon Health and Science University
and Professor Emeritus at Stanford University

We do not know whether this combination GH and IGF-1 treatment is going to be an alternative for these patients, but I think the results are very important and encouraging and look forward to the final data. It may be able to give hope for patients who traditionally do not respond well to GH alone. In my own research poster presented at the meeting, as many as one-third of patients treated with GH alone did not increase by 0.5 SDS. We may have overestimated our ability to help these children. We’ll have to see if combination therapy can help these children because they are taking injections every day for many years, and it is not fair to treat patients if they do not benefit from it.

– Peter Bang, MD, PhD

Associate Professor, Pediatric Endocrinology Unit, Department of Woman and Child Health
Karolinska Institute and University Hospital, Stockholm, Sweden

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