Deferasirox demonstrates a dose-dependent reduction in liver iron concentration and consistent efficacy across subgroups of non-transfusion-dependent thalassemia patients

被引:18
作者
Taher, Ali T. [1 ]
Porter, John B. [2 ]
Viprakasit, Vip [3 ]
Kattamis, Antonis [4 ]
Chuncharunee, Suporn [5 ]
Sutcharitchan, Pranee [6 ,7 ]
Siritanaratkul, Noppadol [3 ]
Galanello, Renzo [8 ]
Karakas, Zeynep [9 ]
Lawniczek, Tomasz [10 ]
Habr, Dany [11 ]
Ros, Jacqueline [10 ]
Zhang, Yiyun [11 ]
Cappellini, M. Domenica [12 ]
机构
[1] Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon
[2] UCL, UCL Canc Inst, Dept Haematol, London, England
[3] Mahidol Univ, Dept Pediat & Internal Med, Siriraj Hosp, Bangkok 10700, Thailand
[4] Univ Athens, Dept Pediat 1, Athens, Greece
[5] Mahidol Univ, Ramathibodi Hosp, Bangkok, Thailand
[6] Chulalongkorn Univ, Bangkok, Thailand
[7] King Chulalongkorn Mem Hosp, Bangkok, Thailand
[8] Osped Reg Microcitemie, Cagliari, Italy
[9] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey
[10] Novartis Pharma AG, Basel, Switzerland
[11] Novartis Pharmaceut, E Hanover, NJ USA
[12] Univ Milan, Dept Internal Med, Ca Granda Fdn IRCCS, Milan, Italy
关键词
OVERLOAD; ALPHA;
D O I
10.1002/ajh.23445
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The 1-year THALASSA study enrolled 166 patients with various non-transfusion-dependent thalassemia (NTDT) syndromes, degrees of iron burden and patient characteristics, and demonstrated the overall efficacy and safety of deferasirox in reducing liver iron concentration (LIC) in these patients. Here, reduction in LIC with deferasirox 5 and 10mg/kg/day starting dose groups is shown to be consistent across the following patient subgroupsbaseline LIC/serum ferritin, age, gender, race, splenectomy (yes/no), and underlying NTDT syndrome (-thalassemia intermedia, HbE/-thalassemia or -thalassemia). These analyses also evaluated deferasirox dosing strategies for patients with NTDT. Greater reductions in LIC were achieved in patients dose-escalated at Week 24 from deferasirox 10mg/kg/day starting dose to 20mg/kg/day. Patients who received an average actual dose of deferasirox >12.517.5mg/kg/day achieved a greater LIC decrease compared with the 7.512.5mg/kg/day and >0<7.5mg/kg/day subgroups, demonstrating a doseresponse efficacy. LIC reduction across patient subgroups was generally consistent with the primary efficacy analysis with a similar safety profile. Am. J. Hematol. 88:503506, 2013. (c) 2013 Wiley Periodicals, Inc.
引用
收藏
页码:503 / 506
页数:4
相关论文
共 20 条
  • [1] ANUWATANAKULCHAI M, 1984, SCAND J HAEMATOL, V32, P153
  • [2] Ascorbate status modulates reticuloendothelial iron stores and response to deferasirox iron chelation in ascorbate-deficient rats
    Brewer, Casey
    Otto-Duessel, Maya
    Lykkesfeldt, Jens
    Nick, Hanspeter
    Wood, John C.
    [J]. EXPERIMENTAL HEMATOLOGY, 2012, 40 (10) : 820 - 827
  • [3] Nontransfusional iron overload in thalassemia intermedia: Role of the hemochromatosis allele
    Cappellini, MD
    Fargion, SR
    Sampietro, M
    Graziadei, G
    Fiorelli, G
    [J]. BLOOD, 1998, 92 (11) : 4479 - 4480
  • [4] Beta-thalassemia
    Galanello, Renzo
    Origa, Raffaella
    [J]. ORPHANET JOURNAL OF RARE DISEASES, 2010, 5
  • [5] Anemia, Ineffective Erythropoiesis, and Hepcidin: Interacting Factors in Abnormal Iron Metabolism Leading to Iron Overload in β-Thalassemia
    Gardenghi, Sara
    Grady, Robert W.
    Rivella, Stefano
    [J]. HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 2010, 24 (06) : 1089 - +
  • [6] α-thalassaemia
    Harteveld, Cornelis L.
    Higgs, Douglas R.
    [J]. ORPHANET JOURNAL OF RARE DISEASES, 2010, 5
  • [7] Iron overload in the Asian community
    Lok, Chun Yu
    Merryweather-Clarke, Alison T.
    Viprakasit, Vip
    Chinthammitr, Yingyong
    Srichairatanakool, Somdet
    Limwongse, Chanin
    Oleesky, David
    Robins, Anthony J.
    Hudson, John
    Wai, Phyu
    Premawardhena, Anuja
    de Silva, H. Janaka
    Dassanayake, Anuradha
    McKeown, Carole
    Jackson, Maurice
    Gama, Rousseau
    Khan, Nasaim
    Newman, William
    Banait, Gurvinder
    Chilton, Andrew
    Wilson-Morkeh, Isaac
    Weatherall, David J.
    Robson, Kathryn J. H.
    [J]. BLOOD, 2009, 114 (01) : 20 - 25
  • [8] Muncie HL, 2009, AM FAM PHYSICIAN, V80, P339
  • [9] Iron overload in non-transfusion-dependent thalassemia: a clinical perspective
    Musallam, Khaled M.
    Cappellini, Maria D.
    Wood, John C.
    Taher, Ali T.
    [J]. BLOOD REVIEWS, 2012, 26 : S16 - S19
  • [10] Elevated liver iron concentration is a marker of increased morbidity in patients with β thalassemia intermedia
    Musallam, Khaled M.
    Cappellini, Maria Domenica
    Wood, John C.
    Motta, Irene
    Graziadei, Giovanna
    Tamim, Hani
    Taher, Ali T.
    [J]. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2011, 96 (11): : 1605 - 1612