Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

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 mu g/l (95% confidence intervals, -1411, -280 mu g/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.