The DEEP project has received research funding from the European Union under the 7th Framework Programme
The clinical history of thalassaemia changed radically since the beginning of the Eighties thanks to the introduction of the iron chelation therapy combined with regular transfusions. The chelation therapy is necessary to eliminate excess iron, preventing its harmful accumulation.
Transfusion therapy, together with iron chelation, have contributed to the increase of the patient’s survival and quality of life, although many serious or life threatening complications continue to affect the thalassaemic population.
The first chelating agent approved for clinical use was deferoxamine (DFO) which still plays a central role in iron overload treatment. Deferoxaminehas satisfactory therapeutic effects and improves the overall survival. However the prognosis remains poor because the requirement for prolonged subcutaneous infusion of the drug make DFO therapy too burdensome for full adherence, thus leading to poor or non-compliance in a high percentage of patients, particularly in the paediatric population. Moreover, 10-15% of subjects are unable to use this chelator due to hypersensitivity or toxic side effects. Finally, socioeconomic reasons (drug distribution, cost, health services availability and organisation) prevent its use in many underdeveloped and developing countries.
Starting from these considerations, in recent years many orally administrable compounds have been studied. Pharmacological research has led to the identification of several interesting molecules but, among these, only two agents have become available in the European Market: deferiprone and deferasirox.
Deferiprone (DFP) was approved as second-line treatment in 1999 and for many years it was the only oral chelator available in Europe for the treatment of subjects for whom deferoxamine was contraindicated or presented serious toxicity. Only recently, a new oral chelator, deferasirox, has been approved as first-line therapy in children from 6 years of age and as second-line therapy for younger children.
The introduction of DFP in the chelation schemes has increased the compliance, the total survival and the quality of life of thalassaemic patients. Comparisons with deferoxamine have shown that both drugs are effective in reducing iron overload, when administered at an appropriate dose. Deferiprone has also shown to be more effective than deferoxamine in removing cardiac iron, thus providing greater protection against iron-induced heart disease, while proportionately to DFP, deferoxamine removes more iron from the liver. These findings have demonstrated that deferiprone represents a valid alternative to the parenteraldeferoxamine and have also stimulated the combined use of the two drugs with the aim to obtain a global improvement in the treatment of iron overload.