A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease

Elliott Vichinsky, Onyinye Onyekwere, John Porter, Paul Swerdlow, James Eckman, Peter Lane, Beatrice Files, Kathryn Hassell, Patrick Kelly, Felicia Wilson, Françoise Bernaudin, Gian Luca Forni, Iheanyi Okpala, Catherine Ressayre-Djaffer, Daniele Alberti, Jaymes Holland, Peter Marks, Ellen Fung, Roland Fischer, Brigitta U Mueller, Thomas Coates, Deferasirox in Sickle Cell Investigators, Elliott Vichinsky, Onyinye Onyekwere, John Porter, Paul Swerdlow, James Eckman, Peter Lane, Beatrice Files, Kathryn Hassell, Patrick Kelly, Felicia Wilson, Françoise Bernaudin, Gian Luca Forni, Iheanyi Okpala, Catherine Ressayre-Djaffer, Daniele Alberti, Jaymes Holland, Peter Marks, Ellen Fung, Roland Fischer, Brigitta U Mueller, Thomas Coates, Deferasirox in Sickle Cell Investigators

Abstract

Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.

Figures

Fig 1
Fig 1
Adjusted change (mean ± SD) in liver iron concentration (LIC) according to assigned treatment category for deferasirox (solid squares) and deferoxamine (DFO, open squares). Statistically significant reductions in LIC were observed with deferasirox in the dose groups treated with 10 (n = 60), 20 (n = 45) and 30 (n = 14) mg/kg with P-values of 0·001, 0·014, and <0·001 respectively.
Fig 2
Fig 2
Change (mean ± SD) in serum ferritin according to assigned baseline liver iron concentration (LIC) category for deferasirox (solid squares) and deferoxamine (DFO, open squares).

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