Safety Outcomes During Pediatric GH Therapy : Final Results From the Prospective GeNeSIS Observational Program
Child, Christopher J. (Eli Lilly and Company, Windlesham, Surrey, United Kingdom)
Zimmermann, Alan G. (Eli Lilly and Company, Indianapolis, Indiana)
Chrousos, George P. (National and Kapodistrian University of Athens, School of Medicine, Athens, Greece)
Cummings, Elisabeth (Dalhousie University/IWK Health Centre, Halifax, Nova Scotia, Canada)
Deal, Cheri L. (University of Montreal and CHU Ste-Justine, Montreal, Quebec, Canada)
Hasegawa, Tomonobu (Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan)
Jia, Nan (Eli Lilly and Company, Indianapolis, Indiana)
Lawrence, Sarah (Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada)
Linglart, Agnès (Hôpital Bicêtre Paris Sud, Paris, France)
Loche, Sandro (Ospedale Pediatrico Microcitemico "A. Cao," AO Brotzu, Cagliari, Italy)
Maghnie, Mohamad (Istituto Giannina Gaslini, University of Genova, Genoa, Italy)
Pérez Sánchez, Jacobo (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Polak, Michel (Hôpital Universitaire Necker Enfants Malades and Université Paris Descartes, Centre des Maladies Endocrines Rares de la Croissance, Paris, France)
Predieri, Barbara (University of Modena and Reggio Emilia, Modena, Italy)
Richter-Unruh, Annette (University Children's Hospital, Bochum, Germany)
Rosenfeld, Ron G. (Oregon Health and Science University, Portland, Oregon)
Yeste Fernández, Diego (Hospital Universitari Vall d'Hebron)
Yorifuji, Tohru (Osaka City General Hospital, Miyakojima-ku, Osaka, Japan)
Blum, Werner F.. (University of Giessen, Giessen, Germany)
Universitat Autònoma de Barcelona

Data:	2018
Resum:	Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy. To assess incidence of key safety outcomes. Prospective, multinational, observational study (1999 to 2015). A total of 22,311 GH-treated children from 827 investigative sites in 30 countries. Children with growth disorders. GH treatment. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) with 95% CIs for mortality, diabetes, and primary cancer using general population registries. Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean ± SD follow-up of 4. 2 ± 3. 2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with an SMR (95% CI) of 0. 61 (0. 44, 0. 82); the SMR was elevated for patients with cancer-related organic GH deficiency [5. 87 (3. 21, 9. 85)]. Based on 18 cases, type 2 diabetes mellitus (T2DM) risk was elevated [SIR: 3. 77 (2. 24, 5. 96)], but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed [SIR: 0. 71 (0. 39, 1. 20)]. Second neoplasms occurred in 31 of 622 cancer survivors [5. 0%; 10. 7 (7. 5, 15. 2) cases/1000 PY] and intracranial tumor recurrences in 67 of 823 tumor survivors [8. 1%; 16. 9 (13. 3, 21. 5) cases/1000 PY]. All three hemorrhagic stroke cases had risk factors. GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) data support the favorable safety profile of pediatric GH treatment. Overall risk of death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared with the general population, but most cases had diabetes risk factors. Safety of GH therapy was assessed in a pediatric observational study. Death and primary cancer rates were not higher than in the general population; T2DM rate was higher owing to risk factors.
Nota:	Altres ajuts: Financial Support: GeNeSIS was sponsored by Eli Lilly and Company (Indianapolis, IN). In compliance with the Uniform Requirements for Manuscripts, established by the International Committee of Medical Journal Editors, the sponsor of this study did not impose any impediment, directly or indirectly, on the publication of the study's results. Disclosure Summary: C.J.C. and N.J. are employees and stockholders ofEliLilly and Company (Indianapolis, IN).W.F.B. and A.G.Z. are former employees and are stockholders of Lilly. C.L.D., T.H., M.M., and R.G.R. are former members of the GeNeSIS International Advisory Board; S.L., J.P.S., A.R.-U., and M.P. have served as regional advisors. B.P. has consulted for Eli Lilly Italia SpA, and E.C. has received grant support from Lilly. W.F.B. also reports heis aconsultant forAmmonett Pharma,Lilly Germany, and Merck KGaA Darmstadt. C.L.D. also reports receipt of grants, consultancy honoraria, and speaker fees from Lilly,EMD Serono, and Sandoz; grants fromOpko Prolor, Pfizer, and Versatis; honoraria and speaker fees from Roche; honoraria from Pfizer; and speaker fees from Novo Nordisk. The remaining authors have nothing to disclose.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	The journal of clinical endocrinology & metabolism, Vol. 104 (september 2018) , p. 379-389, ISSN 1945-7197

DOI: 10.1210/jc.2018-01189
PMID: 30219920

11 p, 746.0 KB

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