Deferasirox demonstrates a dose-dependent reduction in liver iron concentration and consistent efficacy across subgroups of non-transfusion-dependent thalassemia patients

Ali T Taher, John B Porter, Vip Viprakasit, Antonis Kattamis, Suporn Chuncharunee, Pranee Sutcharitchan, Noppadol Siritanaratkul, Renzo Galanello, Zeynep Karakas, Tomasz Lawniczek, Dany Habr, Jacqueline Ros, Yiyun Zhang, M Domenica Cappellini, Ali T Taher, John B Porter, Vip Viprakasit, Antonis Kattamis, Suporn Chuncharunee, Pranee Sutcharitchan, Noppadol Siritanaratkul, Renzo Galanello, Zeynep Karakas, Tomasz Lawniczek, Dany Habr, Jacqueline Ros, Yiyun Zhang, M Domenica Cappellini

Abstract

The 1-year THALASSA study enrolled 166 patients with various non-transfusion-dependent thalassemia (NTDT) syndromes, degrees of iron burden and patient characteristics, and demonstrated the overall efficacy and safety of deferasirox in reducing liver iron concentration (LIC) in these patients. Here, reduction in LIC with deferasirox 5 and 10 mg/kg/day starting dose groups is shown to be consistent across the following patient subgroups-baseline LIC/serum ferritin, age, gender, race, splenectomy (yes/no), and underlying NTDT syndrome (β-thalassemia intermedia, HbE/β-thalassemia or α-thalassemia). These analyses also evaluated deferasirox dosing strategies for patients with NTDT. Greater reductions in LIC were achieved in patients dose-escalated at Week 24 from deferasirox 10 mg/kg/day starting dose to 20 mg/kg/day. Patients who received an average actual dose of deferasirox >12.5-≤17.5 mg/kg/day achieved a greater LIC decrease compared with the ≥7.5-≤12.5 mg/kg/day and >0-<7.5 mg/kg/day subgroups, demonstrating a dose-response efficacy. LIC reduction across patient subgroups was generally consistent with the primary efficacy analysis with a similar safety profile.

Trial registration: ClinicalTrials.gov NCT00873041.

Copyright © 2013 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Forest plots of LSM with 95% confidence interval (CI) for differences in absolute change in LIC from baseline to Week 52 between (A) deferasirox 10 mg/kg/day starting dose and all placebo groups combined; (B) deferasirox 5 mg/kg/day starting dose and placebo groups; and (C) deferasirox 5 mg/kg/day and deferasirox 10 mg/kg/day starting dose groups. *n = 1 missing.
Figure 2
Figure 2
Mean absolute change from baseline in LIC to Week 52 ± SD by (A) baseline LIC category; and (B) baseline serum ferritin category. *The last available post-baseline LIC was carried forward if no LIC value was available at Week 52.

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Source: PubMed

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