Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study.

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

[Deferasirox and Complex Proximal Tubulopathy. Presentation of two clinical cases]. / Deferasirox y Tubulopatía Proximal Compleja. Presentación de dos casos clínicos.

INTRODUCTION: Treatment with iron chelators is essential for patients with iron overload secondary to repeated trans fusions. Deferasirox is the first once-daily oral active iron chelator. As a result, therapeutic adherence has improved, reducing the complications of iron overload, especially heart failure. However, it is not exempt from possible side effects, such as kidney involvement, which is more frequent in children. OBJECTIVE: To report 2 patients with Diamond-Blackfan anemia (DBA) who developed impaired renal function secondary to the administration of Deferasirox. CLINICAL CASES: Case 1. A 15-year-old adolescent diagnosed with DBA undergoing treatment with periodic transfusions and Deferasirox. During an acute gastroenteritis, she developed acute renal failure along with complex proximal tubu- lopathy. Case 2. A 5-year-old boy diagnosed with DBA receiving periodic transfusions and treatment with Deferasirox. He presented polyuria with laboratory abnormalities compatible with acute renal failure and proximal tubular dysfunction. In both cases, they were adequately hydrated and Deferasi rox was temporarily suspended, improving renal function. CONCLUSION: Based on these cases, close monitoring of renal and tubular function, as well as ferritin levels, is recommended in patients recei ving Deferasirox. In the presence of intercurrent processes, adequate hydration should be performed, and an early dose reduction or drug administration interruption should be considered in cases of kidney involvement.

Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome.

Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome

Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr Phase 2 study.

This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.

Two-year analysis of efficacy and safety of deferasirox treatment for transfusional iron overload in sickle cell anemia patients.

The efficacy and safety of a 2-year treatment with deferasirox was evaluated in 31 patients with sickle cell anemia and transfusional iron overload. At 24 months, there were significant decreases from baseline in mean serum ferritin (from 2,344.6 to 1,986.3 µg/l; p = 0.040) and in mean liver iron concentration (from 13.0 ± 5.4 to 9.3 ± 5.7 mg Fe/g dry weight; p < 0.001). Myocardial T2* values were normal (>20 ms) in all patients at baseline and did not change significantly over the course of the study. However, there was a significant improvement from baseline in left ventricular ejection fraction at 24 months (62.2-64.6%; p = 0.02). Deferasirox was generally well tolerated with no progressive increases in serum creatinine or renal failure observed. These data confirm that deferasirox is effective in reducing body iron burden in patients with sickle cell anemia and transfusional iron overload.