Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study

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• 作者：Ali T. Taher^a ; ^{ataher@aub.edu.lb" class="auth_mail" title="E-mail the corresponding author} ; M. Domenica Cappellini^b ; Yesim Aydinok^c ; John B. Porter^d ; Zeynep Karakas^e ; Vip Viprakasit^f ; Noppadol Siritanaratkul^f ; Antonis Kattamis^g ; Candace Wang^h ; Zewen Zhu^h ; Victor Joaquin^h ; Marie José ; Uwamahoroⁱ ; Yong-Rong Lai^j ; ^{laiyongrong@263.net" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AE ; adverse event ; ALT ; alanine aminotransferase ; ANC ; absolute neutrophil count ; CI ; confidence interval ; CrCl ; creatinine clearance ; dw ; dry weight ; Hb ; haemoglobin ; LIC ; liver iron concentration ; LOCF ; last observation carried forward ; MRI ; magnetic resonance imaging ; NTDT ; non-transfusion-dependent thalassaemia ; SAE ; serious AE ; SCr ; serum creatinine ; SD ; standard deviation ; SE ; standard error ; TDT ; transfusion-dependent thalassaemia ; ULN ; upper limit of normal ; UPCR ; urine protein/urine cre
• 刊名：Blood Cells, Molecules and Diseases
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：57
• 期：Complete
• 页码：23-29
• 全文大小：747 K

文摘

Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30 mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10 mg/kg/day. Mean actual dose ± SD over 1 year was 14.70 ± 5.48 mg/kg/day. At week 52, mean LIC ± SD decreased significantly from 15.13 ± 10.72 mg Fe/g dw at baseline to 8.46 ± 6.25 mg Fe/g dw (absolute change from baseline, − 6.68 ± 7.02 mg Fe/g dw [95% CI: − 7.91, − 5.45]; P < 0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n = 6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients.