TY - JOUR
T1 - Long-term safety and efficacy of deferasirox (Exjade®) for up to 5years in transfusional iron-overloaded patients with sickle cell disease
AU - Vichinsky, Elliott
AU - Bernaudin, Françoise
AU - Forni, Gian Luca
AU - Gardner, Renee
AU - Hassell, Kathryn
AU - Heeney, Matthew M.
AU - Inusa, Baba
AU - Kutlar, Abdullah
AU - Lane, Peter
AU - Mathias, Liesl
AU - Porter, John
AU - Tebbi, Cameron
AU - Wilson, Felicia
AU - Griffel, Louis
AU - Deng, Wei
AU - Giannone, Vanessa
AU - Coates, Thomas
PY - 2011/8
Y1 - 2011/8
N2 - 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±6·3mg/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 ≥4years deferasirox exposure significantly decreased by -591μg/l (95% confidence intervals, -1411, -280μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5years 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 4years.
AB - 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±6·3mg/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 ≥4years deferasirox exposure significantly decreased by -591μg/l (95% confidence intervals, -1411, -280μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5years 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 4years.
KW - Deferasirox
KW - Exjade
KW - Iron overload
KW - Oral iron chelator
KW - Sickle cell disease
UR - http://www.scopus.com/inward/record.url?scp=79960204920&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960204920&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2011.08720.x
DO - 10.1111/j.1365-2141.2011.08720.x
M3 - Article
C2 - 21592110
AN - SCOPUS:79960204920
SN - 0007-1048
VL - 154
SP - 387
EP - 397
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -