4.5 Duration of Treatment Treatment should continue until the epiphyses fuse and full growth potential has been achieved. During the course of treatment we monitor patients at regular intervals to check both the progress of growth and occurrence of side effects. Treatment efficacy is assessed through careful monitoring of the growth chart and patient examination. As noted above, substantial catch-up growth may occur with early achievement of a stable therapeutic dose. To maintain efficacy, the dose of

mecasermin should be adjusted for weight gain at regular intervals as growth progresses. Treating physicians should be aware that the typical growth response to mecasermin in SPIGFD is not as robust as the

response Apoptosis inhibitor to GH in patients with GH deficiency. 4.6 Use of Gonadotropin-Releasing Hormone Analogues to Delay Puberty There have been no randomized check details controlled studies of this question. Some children in the mecasermin pivotal study (described by both Chernausek et al. [10] and Backeljauw et al. [14]) did receive these agents. There was no statistically significant difference in adult height between those who were treated with gonadotropin-releasing hormone (GnRH) analogues and those who were not, although it is biologically plausible that combination therapy of mecasermin with GnRH analogues may improve height in SPIGFD patients if the GnRH analogues are started at the onset of puberty [14]. In our opinion, the best way to avoid the issue of puberty leading to truncation of height gain is to begin mecasermin treatment as early as possible, with the caveat that the safety and effectiveness of mecasermin treatment has not been GDC-0449 research buy established in pediatric patients below the age Doxorubicin nmr of 2 years. 5 Conclusion This article illustrates

how the diagnosis of patients with SPIGFD is determined and how this condition can be effectively treated with mecasermin. It is very important to have careful discussions with the family prior to treatment initiation to discuss the necessity of being compliant over the long-term course of therapy, and to educate the family about potential adverse effects. It is also critical when initiating therapy to promptly escalate the dose to the efficacious range >0.1 mg/kg/dose given twice daily, as symptoms allow, and to adjust the dose over time to account for increases in weight as the patient grows. Finally, for patients who had to stop mecasermin as a result of the drug shortage, consideration should be given to reinitiating the original dose escalation scheme when the drug is resumed. Acknowledgments Development of this manuscript was supported by Ipsen Biopharmaceuticals, Inc. Eric Bertelsen, PhD, from Arbor Communications, Inc., and Rosemarie Kelly, PhD, consultant for Ipsen Biopharmaceuticals, Inc., provided writing assistance. Disclosures Dr.