TY - JOUR
T1 - Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia
T2 - The ESCALATOR study
AU - Taher, Ali
AU - El-Beshlawy, Amal
AU - Elalfy, Mohsen S.
AU - Al Zir, Kusai
AU - Daar, Shahina
AU - Habr, Dany
AU - Kriemler-Krahn, Ulrike
AU - Hmissi, Abdel
AU - Al Jefri, Abdullah
PY - 2009/6
Y1 - 2009/6
N2 - Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20-30 mg/kg/d reduces iron burden, depending on transfusional iron intake. Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients ≥2 yr with β-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of ≥3 mg Fe/g dry weight (dw) if baseline LIC was ≥10 mg Fe/g dw, or final LIC of 1-7 mg Fe/g dw for patients with baseline LIC of 2 to <10 mg Fe/g dw. Results: Overall, 233/237 enrolled patients completed 1 yr's treatment. Mean baseline LIC was 18.0 ± 9.1 mg Fe/g dw, while median serum ferritin was 3356 ng/mL. After 1 yr's deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment. Conclusions: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with β-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden.
AB - Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20-30 mg/kg/d reduces iron burden, depending on transfusional iron intake. Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients ≥2 yr with β-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of ≥3 mg Fe/g dry weight (dw) if baseline LIC was ≥10 mg Fe/g dw, or final LIC of 1-7 mg Fe/g dw for patients with baseline LIC of 2 to <10 mg Fe/g dw. Results: Overall, 233/237 enrolled patients completed 1 yr's treatment. Mean baseline LIC was 18.0 ± 9.1 mg Fe/g dw, while median serum ferritin was 3356 ng/mL. After 1 yr's deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment. Conclusions: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with β-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden.
KW - Deferasirox
KW - Iron chelation
KW - Transfusional iron overload
KW - β-thalassaemia
UR - http://www.scopus.com/inward/record.url?scp=65349152022&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65349152022&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0609.2009.01228.x
DO - 10.1111/j.1600-0609.2009.01228.x
M3 - Article
C2 - 19187278
AN - SCOPUS:65349152022
SN - 0902-4441
VL - 82
SP - 458
EP - 465
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 6
ER -