title: Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up.
abstract: Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years' exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β-thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials.gov as #NCT00171210.
authors.affiliation: Universitá di Milano, Ca Granda Foundation Istituto di Ricovero e Cura a Carattere Scientifico [corrected] (IRCCS), Milan, Italy. maria.cappellini@unimi.it
authors.forename: M Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.forename: Leyla
authors.initials: L
authors.lastname: Agaoglu
authors.forename: Duran
authors.initials: D
authors.lastname: Canatan
authors.forename: Marcello
authors.initials: M
authors.lastname: Capra
authors.forename: Alan
authors.initials: A
authors.lastname: Cohen
authors.forename: Guillermo
authors.initials: G
authors.lastname: Drelichman
authors.forename: Marina
authors.initials: M
authors.lastname: Economou
authors.forename: Slaheddine
authors.initials: S
authors.lastname: Fattoum
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
authors.forename: Yurdanur
authors.initials: Y
authors.lastname: Kilinc
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Louis
authors.initials: L
authors.lastname: Griffel
authors.forename: Victor
authors.initials: V
authors.lastname: Dong
authors.forename: Joan
authors.initials: J
authors.lastname: Clark
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aydinok
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000009:adverse effects / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D000077588:Deferasirox; D003676:Deferoxamine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D048788:Growth and Development / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult; D017086:beta-Thalassemia / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox