Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials

PLoS One. 2013 Dec 23;8(12):e82662. doi: 10.1371/journal.pone.0082662. eCollection 2013.

Abstract

Objective: A 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.

Methods: Randomized 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).

Results: Sixteen 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).

Conclusion: Findings indicated that the most effective and safe iron chelators remains to be proven, and further large-scale, long-term studies are needed.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoates / adverse effects*
  • Benzoates / therapeutic use*
  • Deferasirox
  • Deferiprone
  • Deferoxamine / adverse effects*
  • Deferoxamine / therapeutic use*
  • Ferritins / blood
  • Humans
  • Iron / metabolism
  • Iron Chelating Agents / adverse effects
  • Iron Chelating Agents / therapeutic use
  • Liver / metabolism
  • Magnetic Resonance Imaging
  • Myocardium / metabolism
  • Pyridones / adverse effects*
  • Pyridones / therapeutic use*
  • Randomized Controlled Trials as Topic*
  • Stroke Volume
  • Thalassemia / blood
  • Thalassemia / drug therapy*
  • Thalassemia / physiopathology
  • Treatment Outcome
  • Triazoles / adverse effects*
  • Triazoles / therapeutic use*

Substances

  • Benzoates
  • Iron Chelating Agents
  • Pyridones
  • Triazoles
  • Deferiprone
  • Ferritins
  • Iron
  • Deferoxamine
  • Deferasirox

Grants and funding

The funder is Guangdong Medical Insurance Research Association (GDMIRA) http://www.gdmib.com/. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.