title: Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study.
abstract: Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose±SD over 1year was 14.70±5.48mg/kg/day. At week 52, mean LIC±SD decreased significantly from 15.13±10.72mg Fe/g dw at baseline to 8.46±6.25mg Fe/g dw (absolute change from baseline, -6.68±7.02mg Fe/g dw [95% CI: -7.91, -5.45]; P<0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n=6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients.
authors: Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: ataher@aub.edu.lb.
authors: Ali T
authors: AT
authors: Taher
authors: Universitá di Milano, Ca Granda Foundation IRCCS, Milan, Italy.
authors: M Domenica
authors: MD
authors: Cappellini
authors: Department of Paediatric Haematology, Ege University Hospital, Izmir, Turkey.
authors: Yesim
authors: Y
authors: Aydinok
authors: Department of Haematology, University College London, London, UK.
authors: John B
authors: JB
authors: Porter
authors: Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.
authors: Zeynep
authors: Z
authors: Karakas
authors: Department of Pediatrics and Internal Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Vip
authors: V
authors: Viprakasit
authors: Department of Pediatrics and Internal Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Noppadol
authors: N
authors: Siritanaratkul
authors: First Department of Pediatrics, University of Athens, Athens, Greece.
authors: Antonis
authors: A
authors: Kattamis
authors: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors: Candace
authors: C
authors: Wang
authors: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors: Zewen
authors: Z
authors: Zhu
authors: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors: Victor
authors: V
authors: Joaquin
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Marie José
authors: MJ
authors: Uwamahoro
authors: The First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: laiyongrong@263.net.
authors: Yong-Rong
authors: YR
authors: Lai
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects; D001803:Blood Transfusion; D015913:Chelation Therapy / Q000379:methods*; D002648:Child; D000077588:Deferasirox; D003967:Diarrhea / Q000139:chemically induced / Q000175:diagnosis; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019190:Iron Overload / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000175:diagnosis; D013789:Thalassemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000077588:Deferasirox
keywords: Dose escalation; Iron chelation therapy; Iron overload; NTDT; Non-transfusion-dependent thalassaemia