Background: Long-term safety data are reported for paediatric patients treated with recombinant GH (GH; Norditropin®, Novo Nordisk A/S) at the treating physicians discretion and enrolled in the observational NordiNet® International Outcome Study (IOS) (NCT00960128).
Objective and hypotheses: To evaluate incidence rates (IR) (events/1 000 patient-years) of adverse drug reactions (ADR), serious adverse events (SAE), and serious ADR (SADR).
Method: Events were classified by MedDRA Preferred Term/System Organ Class. Patients were categorised by long-term mortality risk (subgroups): low (idiopathic GH deficiency (IGHD)/idiopathic short stature (ISS), 62.4%; small for gestational age (SGA), 37.6%), intermediate (multiple pituitary hormone deficiency, clinically defined syndromes), or high risk (patients treated for malignancy, craniopharyngioma, chronic renal failure). IR during GH treatment were calculated by risk group and mean GH dose up to the event (μg/kg per day; % patients): 020 (4.6%), 2030 (27.2%), 3040 (46.5%), >40 (21.6%).
Results: Data for 15,067 patients (male 57%, mean (SD), baseline age 8.70 (3.89) years; treatment duration, 3.99 (2.90) years) treated during 19982014 were analysed. 342 events were reported in 297 patients. IR for ADR, SAE and SADR were greater in the high- than low-risk group (Table 1), but were similar between the IGHD/ISS and SGA subgroups (3.13, 1.73, 0.61 vs 2.38, 1.77, 0.61 respectively). Five neoplasms/malignancies/cardiovascular events/nervous system disorders were reported in five patients in the low-risk group (benign oral neoplasm, brain neoplasm, T-cell lymphoma, hypotension and benign intracranial hypertension). For all event types, no association between IR and GH dose up to the event was found in any of the risk groups.
|Incidence rate, events/1 000 patient-years (P vs low-risk)|
|Low risk (n=9269)||Intermediate risk (n=4992)||High risk (n=806)|
|ADR||2.85||3.78 (P=0.0544)||8.66 (P<0.0001)|
|SAE||1.74||4.35 (P<0.0001)||12.82 (P<0.0001)|
|SADR||0.61||1.28 (P=0.0101)||4.50 (P<0.0001)|
Conclusion: NordiNet® IOS data show a good safety profile for paediatric GH therapy.
Conflict of interest: LS: member Nordinet® IOS ISC, consult. (Ferring, Novo Nordisk [NN], Merck Serono, Pfizer, Sandoz); grants (MerckSerono, NN, Pfizer). TRR: Nordinet IOS ISC; consultation and speaker fees (Ferring, NN, Merck Serono, Pfizer). OB: Nordinet IOS ISC. EP, BTP: NN employees. M-TS: none
Funding: This study was sponsored by Novo Nordisk Health Care AG.
01 Oct 2015 - 03 Oct 2015