title: Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST).
abstract: BACKGROUND
  Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years.
  
  
  METHODS
  Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study. Patients aged 2 to less than 6 years at enrollment received deferasirox according to local prescribing information, with the primary objective of evaluating safety, specifically renal and hepatic function. Serum ferritin was observed as a surrogate efficacy parameter.
  
  
  RESULTS
  In total, 267 patients (mean age 3.2 years) predominantly with β-thalassemia (n = 176, 65.9%) were enrolled. Mean ± standard deviation deferasirox dose was 25.8 ± 6.5 mg/kg per day over a median of 59.9 months. A total of 145 patients (54.3%) completed 5 years' treatment. The proportion of patients with two or more consecutive postbaseline measurements (≥7 days apart) of serum creatinine higher than age-adjusted upper limit of normal (ULN) and alanine aminotransferase more than five times the ULN was 4.4% (95% confidence interval [CI]: 2.1-7.9) and 4.0% (95% CI: 1.8-7.4), respectively. Median serum ferritin decreased from 1,702 ng/ml at baseline to 1,127 ng/ml at 5 years. There were no new safety signals.
  
  
  CONCLUSIONS
  Safety and efficacy of deferasirox in young pediatric patients in this long-term, observational study in everyday clinical practice were consistent with the known deferasirox profile.
authors.affiliation: UCSF Benioff Children's Hospital & Research Center Oakland, Oakland, California.
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.affiliation: Cairo University, Cairo, Egypt.
authors.forename: Amal
authors.initials: A
authors.lastname: El-Beshlawy
authors.affiliation: Sheikh Khalifa Medical City, Abu Dhabi, UAE.
authors.forename: Azzam
authors.initials: A
authors.lastname: Al Zoebie
authors.affiliation: Centre Hospitalier Intercommunal, Créteil, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Kamdem
authors.affiliation: Chronic Care Center, Hazmieh, Lebanon.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Koussa
authors.affiliation: Songklanagarind Hospital, Songkhla, Thailand.
authors.forename: Thirachit
authors.initials: T
authors.lastname: Chotsampancharoen
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bruederle
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey.
authors.forename: Geralyn
authors.initials: G
authors.lastname: Gilotti
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey.
authors.forename: Jackie
authors.initials: J
authors.lastname: Han
authors.affiliation: Ain Shams University, Cairo, Egypt.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Elalfy
mesh_terms: D001565:Benzoates / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000379:methods; D002675:Child, Preschool; D000077588:Deferasirox; D005260:Female; D006402:Hematologic Diseases / Q000628:therapy; D006486:Hemosiderosis / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D065227:Transfusion Reaction; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox
keywords: deferasirox; hemosiderosis; iron chelation; iron overload; pediatric; real world