Single-center retrospective study of the effectiveness and toxicity of the oral iron chelating drugs deferiprone and deferasirox

BackgroundIron overload, resulting from blood transfusions in patients with chronic anemias, has historically been controlled with regular deferoxamine, but its parenteral requirement encouraged studies of orally-active agents, including deferasirox and deferiprone. Deferasirox, licensed by the US Food and Drug Administration in 2005 based upon the results of randomized controlled trials, is now first-line therapy worldwide. In contrast, early investigator-initiated trials of deferiprone were prematurely terminated after investigators raised safety concerns. The FDA declined market approval of deferiprone; years later, it licensed the drug as “last resort” therapy, to be prescribed only if first-line drugs had failed. We undertook to evaluate the long-term effectiveness and toxicities of deferiprone and deferasirox in one transfusion clinic.Methods and findingsUnder an IRB-approved study, we retrospectively inspected the electronic medical records of consented iron-loaded patients managed between 2009 and 2015 at The University Health Network (UHN), Toronto. We compared changes in liver and heart iron, adverse effects and other outcomes, in patients treated with deferiprone or deferasirox.ResultsAlthough deferiprone was unlicensed in Canada, one-third (n = 41) of locally-transfused patients had been switched from first-line, licensed therapies (deferoxamine or deferasirox) to regimens of unlicensed deferiprone. The primary endpoint of monitoring in iron overload, hepatic iron concentration (HIC), increased (worsened) during deferiprone monotherapy (mean 10±2–18±2 mg/g; p ConclusionsDeferiprone showed ineffectiveness and significant toxicity in most patients. Combination with low doses of first-line therapies did not improve the effectiveness of deferiprone. Exposure to deferiprone, over six years while the drug was unlicensed, in the face of ineffectiveness and serious toxicities, demands review of the standards of local medical practice. The limited scope of regulatory approval of deferiprone, worldwide, should restrict its exposure to the few patients genuinely unable to tolerate the two effective, first-line therapies.