Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST)

Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST)
The oral, once-daily iron chelator deferasirox is indicated for the treatment of adult and pediatric patients with chronic iron overload. However, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years. Therefore, further collection of efficacy and safety data in young patients was necessary.
This observational 5-year ENTRUST study enrolled patients aged 2 to less than 6 years with transfusional hemosiderosis. They received deferasirox according to local prescribing information. The primary objective was the evaluation of safety, specifically renal (serum creatinine) and hepatic (ALT) function. Serum ferritin was also observed as a surrogate efficacy parameter.
267 patients were enrolled. Mean age was 3.2 years. The most frequent diagnosis was 𝛽-thalassemia. 145 patients (54.3%) completed 5 years’ treatment. The proportion of patients with two or more consecutive post-baseline measurements (≥7 days apart) of serum creatinine higher than age-adjusted upper limit of normal (ULN) and ALT more than five times the ULN was 4.4% and 4.0%, respectively. Median serum ferritin decreased from 1,702 ng/ml at baseline to 1,127 ng/ml at 5 years. No new or unexpected safety findings were observed with regard to adverse effects or laboratory abnormalities, with a limited number of patient discontinuations as a direct result of adverse effects.
Almost half of enrolled patients discontinued the study before the end. This is a considerable proportion of the patients enrolled. Even if the main reason of discontinuation was not adverse effects (only 6,7%), it is possible that this high proportion of discontinuations introduced some biases. Also, because this study was observational without predefined therapy protocol, it did not determine if more aggressive therapy could result in a higher incidence of AEs. Finally, this study was funded by Novartis and some of the authors reported consultancy and some research funding from Novartis.
This study provides real-world evidence that supports the manageable safety profile and sustained efficacy of long-term deferasirox therapy in pediatric patients aged 2 to less than 6 years at enrollment with transfusional hemosiderosis.

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