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Inflammation and oxidant-stress in β-thalassemia patients treated with iron chelators deferasirox (ICL670) or deferoxamine: an ancillary study of the Novartis CICL670A0107 trial

¹ Children’s Hospital & Research Center Oakland, Oakland, CA,USA;
² New England Research Institutes, Watertown, MA, USA (current address: Massachusetts General Hospital, Boston, MA);
³ University College London, London, UK;
⁴ Children’s Hospital of Philadelphia, Philadelphia, PA;
⁵ Children’s Hospital Boston, Boston, MA, USA;
⁶ Children’s Hospital Los Angeles, Los Angeles, CA, USA;
⁷ New York-Presbyterian Hospital, New York, NY, USA;
⁸ University Health Network, Toronto, Canada and
⁹ Novartis Pharmaceuticals Corp., East Hanover, NJ, USA

Correspondence: Paul Harmatz, Children’s Hospital & Research Center Oakland, 747 52nd Street, Oakland, Ca, 94609, USA. E-mail:pharmatz{at}mail.cho.org

Background: We assessed whether oxidant-stress and inflammation in β-thalassemia could be controlled by the novel oral iron chelator deferasirox as effectively as by deferoxamine.

Design and Methods: Forty-nine subjects were enrolled from seven sites and studied at baseline, and after 1, 6, and 12 months of therapy. Malondialdehyde, protein carbonyls, vitamins E and C, total non-transferrin bound iron, transferrin saturation, C-reactive protein, cytokines, serum ferritin concentration and liver iron concentration were measured.

Results: Liver iron concentration and ferritin declined significantly in both treatment groups during the study. This paralleled a significant decline in the oxidative-stress marker malondialdehyde (deferasirox –22%/year, deferoxamine –28%/year, average decline p=0.006). The rates of decline did not differ between treatment groups. Malondialdehyde was higher in both treatment groups than in a group of 30 non-thalassemic controls (p<0.001). The inflammatory marker high-sensitivity C-reactive protein decreased significantly only in the group receiving deferasirox (deferasirox –51%/year, deferoxamine +8.5%/year, p=0.02). This result was confounded by a chance difference in the level of high-sensitivity C-reactive protein between the two groups at baseline, but analyses controlling for this difference suggested an equally large treatment effect.

Conclusions: Iron chelation therapy with deferoxamine or with deferasirox was equally effective in decreasing iron burden and malondialdehyde. The possible differential effect of the two chelators on inflammation warrants further investigation.

Key words: iron overload, thalassemia, oxidative stress, inflammation, hsCRP, C-reactive protein, malondialdehyde, lipid peroxidation, vitamin E, vitamin C.