title: Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.
abstract: To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years.
authors: Children's Hospital and Research Center at Oakland, Oakland, CA 94609, USA. evichinsky@mail.cho.org
authors: Elliott
authors: E
authors: Vichinsky
authors: Françoise
authors: F
authors: Bernaudin
authors: Gian Luca
authors: GL
authors: Forni
authors: Renee
authors: R
authors: Gardner
authors: Kathryn
authors: K
authors: Hassell
authors: Matthew M
authors: MM
authors: Heeney
authors: Baba
authors: B
authors: Inusa
authors: Abdullah
authors: A
authors: Kutlar
authors: Peter
authors: P
authors: Lane
authors: Liesl
authors: L
authors: Mathias
authors: John
authors: J
authors: Porter
authors: Cameron
authors: C
authors: Tebbi
authors: Felicia
authors: F
authors: Wilson
authors: Louis
authors: L
authors: Griffel
authors: Wei
authors: W
authors: Deng
authors: Vanessa
authors: V
authors: Giannone
authors: Thomas
authors: T
authors: Coates
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