Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: Two‐year results including pharmacokinetics and concomitant hydroxyurea

• Published in: American journal of hematology Vol. 88; no. 12; pp. 1068 - 1073
• Main Authors: Vichinsky, Elliott, Torres, Marcela, Minniti, Caterina P., Barrette, Stephane, Habr, Dany, Zhang, Yiyun, Files, Beatrice
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2013
• Subjects: Acute Kidney Injury - chemically induced; Adolescent; Adult; Anemia, Sickle Cell - blood; Anemia, Sickle Cell - drug therapy; Anemia, Sickle Cell - therapy; Benzoates - administration & dosage; Benzoates - adverse effects; Benzoates - pharmacokinetics; Benzoates - therapeutic use; Cellulitis - chemically induced; Chelation Therapy - adverse effects; Chemical and Drug Induced Liver Injury - etiology; Child; Child, Preschool; Deferoxamine - administration & dosage; Deferoxamine - adverse effects; Deferoxamine - pharmacokinetics; Deferoxamine - therapeutic use; Drug Therapy, Combination; Female; Ferritins - blood; Hematology; Humans; Hydroxyurea - administration & dosage; Hydroxyurea - adverse effects; Hydroxyurea - pharmacokinetics; Hydroxyurea - therapeutic use; Iron Chelating Agents - administration & dosage; Iron Chelating Agents - adverse effects; Iron Chelating Agents - pharmacokinetics; Iron Chelating Agents - therapeutic use; Iron Overload - drug therapy; Iron Overload - etiology; Male; Middle Aged; Prospective Studies; Transfusion Reaction; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - pharmacokinetics; Triazoles - therapeutic use; Young Adult
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.23569

We report a prospective, randomized, Phase II study of deferasirox and deferoxamine (DFO) in sickle cell disease patients with transfusional iron overload, with all patients continuing on deferasirox after 24 weeks, for up to 2 years. The primary objective was to evaluate deferasirox safety compared with DFO; long‐term efficacy and safety of deferasirox was also assessed. We also report, for the first time, the safety and pharmacokinetics of deferasirox in patients concomitantly receiving hydroxyurea. Deferasirox (n = 135) and DFO (n = 68) had comparable safety profiles over 24 weeks. Adverse events (AEs) secondary to drug administration were reported in 26.7% of patients in the deferasirox cohort and 28.6% in the DFO cohort. Gastrointestinal disorders were more common with deferasirox, including diarrhea (10.4% versus 3.6%) and nausea (5.2% versus 3.6%). The most common AE in the DFO group was injection‐site pain irritation, which occurred in 7% of patients. Acute renal failure occurred in one patient on deferasirox who was continued on medication despite progressive impairment of renal function parameters. Serum ferritin levels were reduced in both treatment groups. Patients continuing on deferasirox for up to 2 years demonstrated an absolute median serum ferritin decrease of −614 ng/mL (n = 96). Increasing deferasirox dose was associated with improved response and a continued manageable safety profile. Concomitant hydroxyurea administration (n = 28) did not appear to influence the efficacy, safety (including liver and kidney function), and pharmacokinetic parameters of deferasirox. Am. J. Hematol. 88:1068–1073, 2013. © 2013 Wiley Periodicals, Inc.