TY - JOUR
TI - Approaching low liver iron burden in chelated patients with non-transfusion-dependent thalassemia: The safety profile of deferasirox
AU - Taher, A.T.
AU - Porter, J.B.
AU - Viprakasit, V.
AU - Kattamis, A.
AU - Chuncharunee, S.
AU - Sutcharitchan, P.
AU - Siritanaratkul, N.
AU - Origa, R.
AU - Karakas, Z.
AU - Habr, D.
AU - Zhu, Z.
AU - Cappellini, M.D.
JO - European Journal of Haematology
PY - 2014
VL - 92
TODO - 6
SP - 521-526
PB - Wiley-Blackwell Publishing Ltd
SN - 0902-4441, 1600-0609
TODO - 10.1111/ejh.12270
TODO - alanine aminotransferase;  creatinine;  deferasirox;  iron;  placebo;  benzoic acid derivative;  deferasirox;  iron;  iron chelating agent;  triazole derivative, abdominal pain;  abnormal laboratory result;  adult;  alanine aminotransferase blood level;  alpha thalassemia;  anorexia;  article;  backache;  beta thalassemia;  clinical article;  controlled study;  coughing;  creatinine blood level;  creatinine clearance;  diarrhea;  drug eruption;  drug fever;  drug safety;  eye disease;  faintness;  female;  follow up;  gastroenteritis;  human;  iron chelation;  iron overload;  lethargy;  liver level;  male;  nausea;  non transfusion dependent thalassemia;  oropharynx pain;  pharyngitis;  post hoc analysis;  priority journal;  randomized controlled trial;  randomized controlled trial (topic);  rhinopharyngitis;  somnolence;  thalassemia;  treatment duration;  upper abdominal pain;  upper respiratory tract infection;  adverse effects;  blood transfusion;  complication;  iron overload;  liver;  metabolism;  pathology;  thalassemia;  treatment outcome, Benzoates;  Blood Transfusion;  Humans;  Iron;  Iron Chelating Agents;  Iron Overload;  Liver;  Thalassemia;  Treatment Outcome;  Triazoles
TODO - Objective: Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over-chelation emerges as patients reach low, near-normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3. Methods: THALASSA was a randomized, double-blind, placebo-controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1-yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end-of-core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2). Results: Mean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure-adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment. Conclusions: The deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over-chelation. © 2014 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.
ER -