Comparative Efficacy and Safety of Deferoxamine, Deferiprone and Deferasirox on Severe Thalassemia: A Meta-Analysis of 16 Randomized Controlled Trials

Sujian Xia,Liting Huang,Hong Jiang,Weidong Zhang,Deepak Shukla

doi:10.1371/journal.pone.0082662

Sujian Xia, Liting Huang + Show 3 more

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https://doi.org/10.1371/journal.pone.0082662

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Journal: PLoS ONE	Publication Date: Dec 23, 2013
Citations: 43	License type: CC BY 4.0

Affiliation: Jinan University, University of Jinan, Novartis (China)

Abstract

ObjectiveA meta-analysis was conducted to investigate the efficacy and safety of three main iron chelators, namely, deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX) for thalassemia major (TM) patients. MethodsRandomized controlled trials comparing mono-therapy DFO, DFP, DFX and combined DFP with DFO therapy in TM patients from January 1990 to December 2012 were searched and selected. Two independent authors assessed data from extracted randomized trials for efficacy and safety in the measurements of serum ferritin (SF), live iron concentration (LIC), myocardial iron content (MIC), left ventricular ejection fraction (LVEF) and adverse events (AEs).ResultsSixteen studies were selected. In the comparison of DFP versus DFO treatment groups, a significant difference was revealed on MIC and LVEF (P=0.01 and P=0.007, respectively) but not on SF or LIC level (P=0.65 and P=0.37, respectively). In comparing combined therapy (DFP plus DFO) versus DFO, a significant difference was shown on MIC and LVEF measurements (P<0.00001 and P=0.003, respectively), but not on SF or LIC levels (P=0.93 and P=0.62, respectively). Moreover, the combined DFP with DFO treatment had significantly higher risk than DFO treatment (RR 1.46 with 95%CI 1.04 to 2.04). When comparing DFX with DFO, a significant difference was shown on the SF level (P=0.003), and there was no difference between DFX and DFO in safety evaluation (RR 1.53 with 95%CI 0.31 to 7.49).ConclusionFindings indicated that the most effective and safe iron chelators remains to be proven, and further large-scale, long-term studies are needed.

Highlights

Thalassemia is a severe genetic blood disorder caused by a mutation in the globin gene leading to the excessive destruction of red blood cells [1]
Study selection and data extraction All studies that were identified by the literature searches were reviewed and selected according to the following prior criteria: (i) patients with thalassemia major regardless of age and sex; (ii) randomized controlled trials (RCTs) with at least two groups comparing with DFO, DFP, DFX or the combination of DFP and DFO; and (iii) outcomes of iron storage or adverse effects in patients
Search results Sixteen RCT studies were included in this meta-analysis with a total of 1,194 patients

Summary

Introduction

Thalassemia is a severe genetic blood disorder caused by a mutation in the globin gene leading to the excessive destruction of red blood cells [1]. It has been estimated that over 42 000 newborns are affected by Beta-thalassemia every year worldwide. Without any aid, such as blood transfusion, Beta-thalassemia major (TM) causes death amongst infected children before the age of 3 years old [2]. Regular blood transfusions can prevent death and decrease mortality. Excessive iron accumulated from transfused red blood cells can lead to organ failure [3,4]. Iron chelation treatment, which can reduce iron store in the body and improve the long-term survival rate of patients with TM, is considered necessary adjuvant therapy

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Conclusion