Efficacy and safety of iron chelators in thalassemia and sickle cell disease: a multiple treatment comparison network meta-analysis and trial sequential analysis.

BACKGROUND: To compare the efficacy and safety of desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) and silymarin in patients with either thalassemia or sickle cell disorder through network meta-analysis.

METHODS: Electronic databases were searched for appropriate randomized clinical trials comparing iron chelators in patients with iron overload. Random effects model was used to generate direct, indirect and mixed treatment comparison pooled estimates for the following outcomes: serum ferritin, liver iron concentration (LIC), changes in serum ferritin, mortality, urine iron excretion, adverse events, neutropenia, agranulocytosis and number of patients withdrawing the chelating therapy.

RESULTS: Thirty-two clinical trials were included in the meta-analysis. DFX/DFO was associated with better serum ferritin levels compared to DFO, DFX, DFO/Silymarin and DFP/DFO. DFX/DFO also lower LIC significantly compared to DFO. DFP/DFO was associated with higher LVEF, low risk of adverse events and reduced end of serum ferritin compared to DFO. Combination of silymarin with either DFP or DFX was observed with reduced end of treatment serum ferritin compared to using either of the drugs alone. DFP was observed with better effects in sickle cell disease. The strength of evidence was very low for most of the comparisons.

CONCLUSION: Relative estimates between the individual iron chelators have been established. However, this evidence should be considered preliminary and may change with the results of future head-to-head clinical trials.