Intérêt des dosages pharmacologiques de Déférasirox en pédiatrie

Abstract : Introduction: Deferasirox (DFX), a once-daily oral iron chelator used since 2006 in France, has improved prognostic and quality of life for pediatric and adult patients under long term transfusionnal program with iron overload. Studies lead on adult patients showed the interest of DFX pharmacologist dosage and defined therapeutic targets. Yet, pediatric studies did not establish recommendations. Aims: to study the effect of DFX concentration on serum ferritin, liver iron concentration (LIC in µmol/g) and myocardial iron overload (T2* in ms) determined by MRI in children. To describe the exposure to DFX stratified on age and pathology. To determine the relationship between residual concentration of DFX and the occurrence of adverse events. Materials and Methods: all patients under 18 at first DFX dosing were included retrospectively; those carrying malign hemopathies were excluded. Clinical and para-clinical data have been collected. The 1st DFX residual dosing, performed after at least 3 months of treatment, the ferritin measurement performed after 6 months and the hepatic and cardiac MRI after 12 months of treatment have been analyzed. Patients have been included in groups good or bad responders, depending on serum ferritin (below or above 500 µg/l), LIC (below or above 200 µmol/g) and T2* (below or above 20 ms). Results: two hundred and thirty eight dosing have been collected on 66 patients (including 27 β-thalassaemia major, 22 sickle-cell anemia, 5 Blackfan-Diamond anemia (BDA)). Exposure to DFX was significantly lower in children under 6, and higher in β-thalassaemia major and BDA patients. Median DFX residual concentration was higher in good responders on serum ferritin (27 vs. 8µg/ml, p 0.02), as well as the one of LIC (20.9 vs. 10.9 µg/ml, p 0.04), but not in T2*. Serum creatinin increase has been linked to a higher residual concentration (28.2 vs. 11.4 µg/ml, p 0.01). Conclusion: in children treated for secondary iron overload, target for DFX residual concentration associated with a good response seems to be higher than what has been observed on adult. To optimize earlier serum ferritin and MRI under treatment, avoiding toxicity, it is recommended to regularly monitor DFX concentration.
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Master Thesis
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Lucile Espeso. Intérêt des dosages pharmacologiques de Déférasirox en pédiatrie. Médecine humaine et pathologie. 2017. ⟨dumas-01628631⟩

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