International Journal of Hematology

, Volume 98, Issue 4, pp 406–416

Long-term efficacy and safety of eculizumab in Japanese patients with PNH: AEGIS trial

  • Yuzuru Kanakura
  • Kazuma Ohyashiki
  • Tsutomu Shichishima
  • Shinichiro Okamoto
  • Kiyoshi Ando
  • Haruhiko Ninomiya
  • Tatsuya Kawaguchi
  • Shinji Nakao
  • Hideki Nakakuma
  • Jun-ichi Nishimura
  • Taroh Kinoshita
  • Camille L. Bedrosian
  • Keiya Ozawa
  • Mitsuhiro Omine
Original Article

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, progressive hematopoietic stem cell disorder characterized by chronic complement-mediated hemolysis leading to life-threatening complications and early mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal complement activation, reduces hemolysis, decreases the risk of thrombosis, and improves renal function and quality of life in PNH patients. The long-term efficacy and safety of eculizumab in Japanese patients were assessed in a 2-year extension to a 12-week, open-label study (AEGIS). Eculizumab treatment led to an immediate and sustained reduction in intravascular hemolysis (P < 0.001) and red blood cell transfusions (P = 0.0016) compared with baseline levels. There were no reports of thromboembolism during eculizumab treatment. The majority of patients had stable (56 %) or improved (41 %) renal function and an improved quality of life (P = 0.015), with sustained reductions in fatigue and dyspnea. Eculizumab was well tolerated; no deaths or serious hemolytic events were reported, and the rate of infections declined over time. There were no significant differences in the response to eculizumab in patients with or without bone marrow dysfunction. These results demonstrate that eculizumab is an effective, well-tolerated long-term treatment for Japanese PNH patients and leads to continued amelioration of some hemolytic complications.

Keywords

Paroxysmal nocturnal hemoglobinuria Complement-inactivating agents Hemolysis Eculizumab Hematopoietic stem cell 

Copyright information

© The Japanese Society of Hematology 2013

Authors and Affiliations

  • Yuzuru Kanakura
    • 1
  • Kazuma Ohyashiki
    • 2
  • Tsutomu Shichishima
    • 3
  • Shinichiro Okamoto
    • 4
  • Kiyoshi Ando
    • 5
  • Haruhiko Ninomiya
    • 6
  • Tatsuya Kawaguchi
    • 7
  • Shinji Nakao
    • 8
  • Hideki Nakakuma
    • 9
  • Jun-ichi Nishimura
    • 10
  • Taroh Kinoshita
    • 11
  • Camille L. Bedrosian
    • 12
  • Keiya Ozawa
    • 13
  • Mitsuhiro Omine
    • 14
  1. 1.Department of Hematology and OncologyOsaka University HospitalSuitaJapan
  2. 2.Tokyo Medical UniversityTokyoJapan
  3. 3.Department of Cardiology and Hematology, School of MedicineFukushima Medical UniversityFukushimaJapan
  4. 4.Division of Hematology, Department of Internal MedicineKeio University HospitalTokyoJapan
  5. 5.Department of Hematology and OncologyTokai University School of MedicineIseharaJapan
  6. 6.Institute of Clinical MedicineUniversity of TsukubaTsukubaJapan
  7. 7.Second Department of Internal MedicineKumamoto University School of MedicineKumamotoJapan
  8. 8.Department of Hematology and OncologyKanazawa University HospitalKanazawaJapan
  9. 9.Department of Hematology/OncologyWakayama Medical UniversityWakayamaJapan
  10. 10.Department of Hematology and Oncology, Graduate School of MedicineOsaka UniversitySuitaJapan
  11. 11.Department of Immunoregulation, Research Institute for Microbial DiseasesOsaka UniversitySuitaJapan
  12. 12.Alexion PharmaceuticalsCambridgeUSA
  13. 13.Division of HematologyJichi Medical UniversityShimotsukeJapan
  14. 14.Division of HematologyShowa University Fujigaoka HospitalYokohamaJapan

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