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

Abstract

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.

• Authors: Janet L Kwiatkowski, Mona Hamdy, Amal El-Beshlawy, Fatma S E Ebeid, Mohammed Badr, Abdulrahman Alshehri, Julie Kanter, Baba Inusa, Amira A M Adly, Suzan Williams, Yurdanur Kilinc, David Lee, Fernando Tricta, Mohsen S Elalfy
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 4 Pg. 1243-1254 (02 22 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 34847228 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Iron Chelating Agents
• Pyridones
• Deferiprone
• Transferases
• Deferoxamine

Topics

• Adolescent
• Anemia, Sickle Cell (complications, drug therapy)
• Blood Transfusion
• Deferiprone (therapeutic use)
• Deferoxamine (adverse effects)
• Female
• Humans
• Iron Chelating Agents (adverse effects)
• Iron Overload (drug therapy, etiology)
• Male
• Pyridones (adverse effects)
• Thalassemia (complications, drug therapy)
• Transferases