ESPE Abstracts (2016) 86 RFC15.6

Safety of GH in Paediatrics: The GeNeSIS Prospective Observational Study Experience between 1999 and 2015 (NCT01088412)

Werner Bluma, Christopher Childb, George Chrousosc, Elisabeth Cummingsd, Cheri Deale, Tomonobu Hasegawaf, Paul-Martin Holterhusg, Nan Jiah, Sarah Lawrencei, Agnès Linglartj, Sandro Lochek, Mohamad Maghniel, Jacobo Pérez Sánchezm, Michel Polakn,o, Barbara Predierip, Annette Richter-Unruhq, Ron Rosenfeldr, Toshihiro Tajimas, Diego Yestet & Tohru Yorifujiu

aUniversity of Giessen, Giessen, Germany; bEli Lilly and Company, Windlesham, Surrey, UK; cUniversity of Athens School of Medicine, Athens, Greece; dDalhousie University/IWK Health Centre, Halifax, Nova Scotia, Canada; eUniversity of Montreal and CHU Ste-Justine, Montreal, Quebec, Canada; fKeio University School of Medicine, Shinjuku-ku, Tokyo, Japan; gChristian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany; hEli Lilly and Company, Indianapolis, Indiana, USA; iChildren’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; jHôpital Bicêtre Paris Sud, Paris, France; kOspedale Paediatrico Microcitemico, AOB Cagliari, Cagliari, Italy; lIstituto Giannina Gaslini, University of Genova, Genova, Italy; mCorporació Sanitària Parc Taulí, Sabadell, Spain; nHôpital Universitaire Necker Enfants Malades, Paris, France; oUniversité Paris Descartes, Centre des Maladies Endocrines Rares de la Croissance, Paris, France; pUniversity of Modena and Reggio Emilia, Modena, Italy; qUniversity of Münster, Münster, Germany; rOregon Health and Science University, Portland, Oregon, USA; sJichi Children’s Medical Center Tochigi, Shimotsuke-shi, Tochigi, Shimotsuke-shi, Tochigi, Japan; tHospital Vall d’Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain; uOsaka City General Hospital, Miyakojima-ku, Osaka, Japan

Background: Although GH’s safety profile since 1987 is good, concerns remain regarding cancer (CA) risk, and French SAGhE data indicated increased mortality and cerebrovascular disease (CVD) in certain GH-treated patients (pts).

Objective and hypotheses: To evaluate key safety outcome incidence in GH-treated pts of all short stature diagnoses (dx) who participated in GeNeSIS (1999–2015, 30 countries).

Methods: Pt history/case ascertainment required review of study and corporate pharmacovigilance databases. Person-years (PY) of follow-up were calculated between first and last contacts (later of event onset, last study visit or summary date). Standardised mortality (SMR) and incidence (SIR) ratios were calculated using expected cases from contemporary general population registries (CDC, GLOBOCAN, SEER, SEARCH for Diabetes in Youth, WHO) adjusted for country, age, sex and ethnicity (where applicable).

Results: Amongst 21178 pts eligible for analysis the predominant short stature dx were GH deficiency (63%), idiopathic short stature (13%), Turner syndrome (8%) and small for gestational age (6%). Mean±SD study entry age was 10.5±3.8Y and duration of follow-up was 4.4±3.2Y (~92,000PY). The table shows cases, crude incidence and SMR/SIR for key outcomes. SMRs were not elevated for any specific dx except for pts with organic GH deficiency due to previous (prev) CA (SIR, 95%CI 5.87, 3.21–9.85). Most pts with incident type 2 diabetes (T2DM) had risk factors (incl. syndromic dx, prev irradiation, obesity). Haemorrhagic CVD occurred in 2 intracranial tumour (ICT) survivors and after renal transplant in 1 pt with renal insufficiency.

Table 1. (for abstract RFC15.6)
OutcomePts at riskN affected/N at risk (%)Affected/1000 PY, 95% CISMR/SIR, 95% CI
Any eventAll6365/21178 (30.1)
DeathAll42/21178 (0.20)0.46, 0.34–0.620.61, 0.44–0.82
CVDAll16/21178 (0.08)0.17, 0.11–0.28
HaemorrhagicAll3/21178 (0.01)0.03, 0.01–0.10
T2DMAll18/21178 (0.08)0.20, 0.12–0.313.79, 2.25–6.00
1st CANo prev CA14/20556 (0.07)0.16, 0.09–0.270.71, 0.39–1.20
ICT recurrencePrev ICT67/823 (8.14)16.9, 13.3–21.5
2nd neoplasmPrev CA31/622 (4.98)10.7, 7.5–15.2

Conclusion: Acknowledging the limited GeNeSIS follow-up duration, no increased risk for death or 1st CA was observed, and no strokes were recorded in dx studied in published SAGhE analyses. SIRs for T2DM were elevated so glucose monitoring of GH-treated pts with risk factors is recommended. All pts with prev ICT/CA should be monitored for recurrence/2nd neoplasm whether treated or not with GH.

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