International Journal of Hematology

, Volume 93, Issue 3, pp 319–328 | Cite as

Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox

  • Vip Viprakasit
  • Hishamshah Ibrahim
  • Shau-Yin Ha
  • Phoebe Joy Ho
  • Chi-Kong Li
  • Lee-Lee Chan
  • Chang-Fang Chiu
  • Pranee Sutcharitchan
  • Dany Habr
  • Gabor Domokos
  • Bernard Roubert
  • Hong-Ling Xue
  • Donald K. Bowden
  • Kai-Hsin Lin
Original Article

Abstract

Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients’ Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.

Keywords

Thalassaemia Iron chelation therapy Asia-Pacific Serum ferritin Skin rash 

Notes

Acknowledgments

The authors would like to thank Suresh Vutukuru for statistical support and Hui-Hwa Choo for medical editorial assistance with this manuscript. V.V. is supported by Thailand Research Fund & BIOTEC, Thailand. Novartis Pharma provided sponsorship for the EPIC study and financial support for medical editorial assistance of this manuscript.

Conflict of interest

None.

Supplementary material

12185_2011_789_MOESM1_ESM.doc (85 kb)
Supplementary material 1 (DOC 85 kb)

References

  1. 1.
    Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008;86:480–7.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79:704–12.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Viprakasit V, Tanphaichitr VS, Mahasandana C, et al. Linear growth in homozygous beta-thalassaemia and beta-thalassaemia/hemoglobin E patients under different treatment regimens. J Med Assoc Thai. 2001;84:929–41.PubMedGoogle Scholar
  4. 4.
    Viprakasit V, Tanphaichitr VS, Chinchang W, et al. Evaluation of alpha hemoglobin stabilizing protein (AHSP) as a genetic modifier in patients with beta thalassaemia. Blood. 2004;103:3296–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Weatherall DJ, Clegg JB. The thalassaemia syndromes. 4th ed. Oxford: Blackwell Science; 2001.CrossRefGoogle Scholar
  6. 6.
    Cappellini MD, Cohen A, Eleftheriou A, et al. Guidelines for the clinical management of thalassaemia. 2nd ed. Cyprus: Thalassaemia International Federation; 2007.Google Scholar
  7. 7.
    Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341:1986–95.CrossRefPubMedGoogle Scholar
  8. 8.
    Ishizaka N, Saito K, Mitani H, et al. Iron overload augments angiotensin II-induced cardiac fibrosis and promotes neointima formation. Circulation. 2002;106:1840–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Ehlers KH, Giardina PJ, Lesser ML, et al. Prolonged survival in patients with beta-thalassaemia major treated with deferoxamine. J Pediatr. 1991;118:540–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Brittenham GM, Griffith PM, Nienhuis AW, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassaemia major. N Engl J Med. 1994;331:567–73.CrossRefPubMedGoogle Scholar
  11. 11.
    Borgna-Pignatti C, Rugolotto S, De SP, et al. Survival and complications in patients with thalassaemia major treated with transfusion and deferoxamine. Haematologica. 2004;89:1187–93.PubMedGoogle Scholar
  12. 12.
    Viprakasit V, Lee-Lee C, Chong QT, et al. Iron chelation therapy in the management of thalassaemia: the Asian perspectives. Int J Hematol. 2009;90:435–45.CrossRefPubMedGoogle Scholar
  13. 13.
    Chen AC, Peng CT, Wu SF, et al. Effect of deferiprone on liver iron overload and fibrosis in hepatitis-C-virus-infected thalassaemia. Hemoglobin. 2006;30:209–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Ha SY, Chik KW, Ling SC, Lee, et al. A randomized controlled study evaluating the safety and efficacy of deferiprone treatment in thalassaemia major patients from Hong Kong. Hemoglobin. 2006;30:263–74.CrossRefPubMedGoogle Scholar
  15. 15.
    Peng CT, Wu KH, Wu SF, et al. Deferiprone or deferoxamine vs combination therapy in patients with beta-thalassaemia major: a case study in Taiwan. Hemoglobin. 2006;30:125–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Miyazawa K, Ohyashiki K, Urabe A, et al. A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan. Int J Hematol. 2008;88:73–81.CrossRefPubMedGoogle Scholar
  17. 17.
    Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassaemia. Blood. 2006;107:3455–62.CrossRefPubMedGoogle Scholar
  18. 18.
    Galanello R, Piga A, Forni GL, et al. Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with beta-thalassaemia major. Haematologica. 2006;91:1343–51.PubMedGoogle Scholar
  19. 19.
    Piga A, Galanello R, Forni GL, et al. Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassaemia patients with transfusional iron overload. Haematologica. 2006;91:873–80.PubMedGoogle Scholar
  20. 20.
    Taher A, El-Beshlawy A, Elalfy MS, et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia: the ESCALATOR study. Eur J Haematol. 2009;82:458–65.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Viprakasit V, Sripornsawan P, Pongthanakul B, et al. Evaluation of adverse events due to deferasirox, a novel oral iron chelator, in 79 Thai pediatric patients with beta-thalassaemia. In: The 9th Cooley’s Anemia Symposium. The New York Academy of Sciences; 2009;9:27.Google Scholar
  22. 22.
    Cappellini MD, Porter J, El-Beshlawy A, et al. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica. 2010;95:557–66.CrossRefPubMedGoogle Scholar
  23. 23.
    Chan JC, Chim CS, Ooi CG, et al. Use of the oral chelator deferiprone in the treatment of iron overload in patients with Hb H disease. Br J Haematol. 2006;133:198–205.CrossRefPubMedGoogle Scholar
  24. 24.
    Peng CT, Chang JS, Wang LY, et al. Update on thalassaemia treatment in Taiwan, including bone marrow transplantation, chelation therapy, and cardiomyopathy treatment effects. Hemoglobin. 2009;33:304–11.CrossRefPubMedGoogle Scholar
  25. 25.
    Cohen AR, Galanello R, Piga A, et al. Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood. 2003;102:1583–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Cohen AR, Glimm E, Porter JB. Effect of transfusional iron intake on response to chelation therapy in beta-thalassaemia major. Blood. 2008;111:583–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Porter JB. Optimizing iron chelation strategies in beta-thalassaemia major. Blood Rev. 2009;23(Suppl 1):S3–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Vichinsky E. Clinical application of deferasirox: practical patient management. Am J Hematol. 2008;83:398–402.CrossRefPubMedGoogle Scholar
  29. 29.
    Chung WH, Hung SI, Chen YT. Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2007;7:317–23.CrossRefPubMedGoogle Scholar
  30. 30.
    Payne PW Jr. For Asians only? The perils of ancestry-based drug prescribing. J Law Med Ethics. 2008;36:585–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Tassaneeyakul W, Jantararoungtong T, Chen P, et al. Strong association between HLA-B*5801 and allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics. 2009;19:704–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Gattermann N, Finelli C, Porta MD, et al. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: results from the large 1-year EPIC study. (2010) Leuk Res. 2010;34(9):1143–50.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Vip Viprakasit
    • 1
  • Hishamshah Ibrahim
    • 2
  • Shau-Yin Ha
    • 3
  • Phoebe Joy Ho
    • 4
  • Chi-Kong Li
    • 5
  • Lee-Lee Chan
    • 6
  • Chang-Fang Chiu
    • 7
  • Pranee Sutcharitchan
    • 8
  • Dany Habr
    • 9
  • Gabor Domokos
    • 10
  • Bernard Roubert
    • 10
  • Hong-Ling Xue
    • 11
  • Donald K. Bowden
    • 12
  • Kai-Hsin Lin
    • 13
  1. 1.Haematology-Oncology Division, Department of Paediatrics and Thalassaemia Center, Faculty of MedicineSiriraj Hospital, Mahidol UniversityBangkokThailand
  2. 2.Hospital Kuala LumpurKuala LumpurMalaysia
  3. 3.Queen Mary Hospital, The University of Hong KongHong KongHong Kong
  4. 4.Royal Prince Alfred HospitalSydneyAustralia
  5. 5.Prince of Wales Hospital, Chinese University of Hong KongHong KongHong Kong
  6. 6.University Malaya Medical CentreKuala LumpurMalaysia
  7. 7.China Medical University HospitalTaichungTaiwan
  8. 8.Chulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand
  9. 9.Novartis Pharmaceuticals CorpEast HanoverUSA
  10. 10.Novartis Pharma AGBaselSwitzerland
  11. 11.Novartis Asia Pacific PharmaceuticalsSingaporeSingapore
  12. 12.Monash Medical CentreMelbourneAustralia
  13. 13.National Taiwan University HospitalTaipeiTaiwan

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