Twice daily deferasirox significantly improves clinical efficacy in transfusion dependent thalassaemias who were inadequate responders to standard once daily dose

摘要

The clinical efficacy of deferasirox (DFX), a once daily oral iron chelator, in patients with transfusion iron overload depends on factors such as iron burden, rate of red cell transfusions, and appropriate dose of the drug [1], At present, the recommended dose is 30 mg/kg/day, though doses of up to 40 mg/kg per day are suggested in patients with cardiac siderosis with acceptable safety profiles in patients with cardiac siderosis. The pharmacokinetic/pharmacodynamic parameters of deferasirox are similar among different ethnic groups [2], Moreover, our sub-group analysis showed that the clinical efficacy of DFX for patients in the Pacific Asian region did not differ from the rest of the world [3]. However, these conclusions were limited by the number of patients studied, often in uncontrolled trials. In a non-clinical trial setting, 22 to 30% of patients did not achieve satisfactory iron balance at a dose of >30 mg/kg per day [4,5], These patients were labeled inadequate responders. In our center, surprisingly 44% of transfusion dependent thalassaemia patients were classified as inadequate responders to DFX since the drug was registered in 2007. A difference in bioavailability of each inadequate responder was the principal mechanism identified [5]. We examined whether adjusting DFX from once daily (QD) into two dividing dose per day (BID) would improve drug absorption and therapeutic efficacy in such patients.