Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia

1-Year results from a prospective, randomized, double-blind, placebo-controlled study

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

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. Atotal of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, -2.33 ± 0.7 mg Fe/g dry weight [dw], P = .001, and -4.18 ± 0.69 mg Fe/g dw, P <.001) for the 5 and 10 mg/kg/d deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM -235 and -337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P <.001). In the placebo patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and 115 ng/mL (LSM), respectively. The most common drug-related adverse events were nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is the first randomized study showing that iron chelation with deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo.

Original languageEnglish
Pages (from-to)970-977
Number of pages8
JournalBlood
Volume120
Issue number5
DOIs
Publication statusPublished - Aug 2 2012

Fingerprint

Iron Overload
Thalassemia
Iron
Placebos
Least-Squares Analysis
Weights and Measures
Ferritins
Liver
Chelation
deferasirox
Exanthema
Drug-Related Side Effects and Adverse Reactions
Serum
Nausea
Diarrhea
Safety
Scanning electron microscopy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia : 1-Year results from a prospective, randomized, double-blind, placebo-controlled study. / Taher, Ali T.; Porter, John; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Galanello, Renzo; Karakas, Zeynep; Lawniczek, Tomasz; Ros, Jacqueline; Zhang, Yiyun; Habr, Dany; Cappellini, Maria Domenica.

In: Blood, Vol. 120, No. 5, 02.08.2012, p. 970-977.

Research output: Contribution to journalArticle

Taher, AT, Porter, J, Viprakasit, V, Kattamis, A, Chuncharunee, S, Sutcharitchan, P, Siritanaratkul, N, Galanello, R, Karakas, Z, Lawniczek, T, Ros, J, Zhang, Y, Habr, D & Cappellini, MD 2012, 'Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-Year results from a prospective, randomized, double-blind, placebo-controlled study', Blood, vol. 120, no. 5, pp. 970-977. https://doi.org/10.1182/blood-2012-02-412692
Taher, Ali T. ; Porter, John ; Viprakasit, Vip ; Kattamis, Antonis ; Chuncharunee, Suporn ; Sutcharitchan, Pranee ; Siritanaratkul, Noppadol ; Galanello, Renzo ; Karakas, Zeynep ; Lawniczek, Tomasz ; Ros, Jacqueline ; Zhang, Yiyun ; Habr, Dany ; Cappellini, Maria Domenica. / Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia : 1-Year results from a prospective, randomized, double-blind, placebo-controlled study. In: Blood. 2012 ; Vol. 120, No. 5. pp. 970-977.
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