Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

Abstract

BACKGROUND: Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. METHODS: The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using chi2. RESULTS: Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4). The degree of improvement was also larger with desferrioxamine. CONCLUSIONS: This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis - despite its limitations - should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients.

Figure 1

Initial and final hepatic iron concentrations for the 98 patients included in the main analyses by treatment and dose category. Hepatic iron concentrations are expressed in mg/g dry liver weight. The dotted lines indicate the cut-off (7.0 mg/g) above which patients run an increased risk for complications due to hepatic iron overload.

Figure 2

Odds ratios for improvement in hepatic iron concentrations over time, presented on a logarithmic scale. The odds ratios for the main analysis are provided for each dose category of L1 separately and combined. The odds ratios for the sensitivity analysis are presented for inclusion of each of the additional studies one by one and combined.