C. M. Lopez1, D. Solomon1, R. A. Cowles1, D. E. Ozgediz1, D. H. Stitelman1, M. G. Caty1, E. R. Christison-Lagay1 1Yale University School Of Medicine,Department Of Surgery, Section Of Pediatric Surgery,New Haven, CT, USA
Introduction: Gonadotropin releasing hormone (GnRH) agonists are FDA approved for the treatment of precocious puberty. Therapy consists of either histrelin acetate (Supprelin, Endo Pharmaceuticals), a surgically implanted device seen as the preferred form of treatment, or leuprolide acetate (Lupron Depot, Abbvie) injections. In recent years, the use of these agents has been extended to include the “off-label” treatment of a heterogeneous group of pediatric conditions with normally timed puberty including hyperandrogenism, endometriosis, short stature, and gender dysphoria. We sought to investigate the trends in the “off-label” use of GnRH agonists among pediatric patients, hypothesizing that “off-label” usage would preferentially favor those patients covered by commercial insurers.
Methods: We analyzed data on the use of Supprelin and Lupron reported to the Pediatric Health Information System (PHIS) from 2013 to 2016. Demographic information and payer status were collected. ICD-9 and ICD-10 diagnostic codes were analyzed to determine whether the indication for therapy was for precocious puberty (“on-label use”) or for other diagnostic codes (“off-label use”).
Results: 39 children’s hospitals within the PHIS provided outpatient surgical and billing data on the administration of GnRH agonist therapies during the study period. During this period, the annual number of unique pediatric patients treated with GnRH agonists for precocious puberty increased modestly, from 283 to 303; meanwhile, the number of procedures for an off-label indication more than tripled from 39 to 125. The increasing use of the Supprelin implants to treat short stature and gender dysphoria were largely responsible for this increase in off-label use, the former increasing from 10 to 46 patients and the latter from 3 to 57 patients over the study period.
When compared to the distribution of patients treated for precocious puberty, commercially insured patients were more likely to receive GnRH agonists for an off-label indication (p=0.047) than those qualifying for public insurance. This disparity was more pronounced in those in whom GnRH agonists were being used to treat short stature or gender dysphoria (p=0.028).
Conclusion: From 2013 to 2016, off-label use of GnRH agonists in children increased more than threefold with the greatest increases seen in the treatment of short stature and gender dysphoria. Patients treated for these conditions were more likely to be privately insured than the larger cohort of patients receiving on-label treatment for precocious puberty, thus identifying a potential disparity in access to care which requires future investigation.