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Long‐term safety and efficacy of deferasirox (Exjade ® ) for up to 5 years in transfusional iron‐overloaded patients with sickle cell disease
Author(s) -
Vichinsky Elliott,
Bernaudin Françoise,
Forni Gian Luca,
Gardner Renee,
Hassell Kathryn,
Heeney Matthew M.,
Inusa Baba,
Kutlar Abdullah,
Lane Peter,
Mathias Liesl,
Porter John,
Tebbi Cameron,
Wilson Felicia,
Griffel Louis,
Deng Wei,
Gian Vanessa,
Coates Thomas
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08720.x
Subject(s) - deferasirox , medicine , discontinuation , adverse effect , renal function , nausea , deferoxamine , dosing , deferiprone , gastroenterology , pediatrics , surgery , thalassemia
Summary 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.