title: Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study.
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. A total 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.
authors.affiliation: American University of Beirut, Beirut, Lebanon. ataher@aub.edu.lb
authors.forename: Ali T
authors.initials: AT
authors.lastname: Taher
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
authors.forename: Suporn
authors.initials: S
authors.lastname: Chuncharunee
authors.forename: Pranee
authors.initials: P
authors.lastname: Sutcharitchan
authors.forename: Noppadol
authors.initials: N
authors.lastname: Siritanaratkul
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Karakas
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lawniczek
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ros
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D001565:Benzoates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001803:Blood Transfusion; D002648:Child; D000077588:Deferasirox; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D019190:Iron Overload / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies; D013789:Thalassemia / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D010919:Placebos; D014230:Triazoles; D000077588:Deferasirox