title: Importance of optimal dosing ≥ 30 mg/kg/d during deferasirox treatment: 2.7-yr follow-up from the ESCALATOR study in patients with β-thalassaemia.
abstract: Following 1-yr deferasirox therapy in the ESCALATOR study, 57% of previously chelated patients with β-thalassaemia achieved treatment success (maintenance of or reduction in liver iron concentration (LIC) vs. baseline LIC). Seventy-eight per cent had dose increases at median of 26 wk, suggesting that 1-yr results may not have reflected full deferasirox efficacy. Extension data are presented here. Deferasirox starting dose was 20 mg/kg/d (increases to 30/40 mg/kg/d permitted in the core/extension, respectively). Efficacy was primarily assessed by absolute change in LIC and serum ferritin. Overall, 231 patients received deferasirox in the extension; 67.4% (P < 0.0001) achieved treatment success. By the end of the extension, 66.2% of patients were receiving doses ≥ 30 mg/kg/d. By the end of the 1-yr extension, mean LIC had decreased by 6.6 ± 9.4 mg Fe/g dw (baseline 19.6 ± 9.2; P < 0.001) and median serum ferritin by 929 ng/mL (baseline 3356; P < 0.0001). There was a concomitant improvement in liver function markers (P < 0.0001). Fewer drug-related adverse events were reported in extension than core study (23.8% vs. 44.3%). Doses ≥ 30 mg/kg/d were generally required because of high transfusional iron intake and high baseline serum ferritin levels, highlighting the importance of administering an adequate dose to achieve net negative iron balance.
authors.affiliation: American University of Beirut Medical Center, Beirut, Lebanon. ataher@aub.edu.lb
authors.forename: Ali
authors.initials: A
authors.lastname: Taher
authors.forename: Mohsen S
authors.initials: MS
authors.lastname: Elalfy
authors.forename: Kusai
authors.initials: K
authors.lastname: Al Zir
authors.forename: Shahina
authors.initials: S
authors.lastname: Daar
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Jefri
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kriemler-Krahn
authors.forename: Ali
authors.initials: A
authors.lastname: El-Ali
authors.forename: Bernard
authors.initials: B
authors.lastname: Roubert
authors.forename: Amal
authors.initials: A
authors.lastname: El-Beshlawy
mesh_terms: D001565:Benzoates / Q000627:therapeutic use*; D000077588:Deferasirox; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D014230:Triazoles / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox