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

Int J Hematol. 2013 Oct;98(4):406-16. doi: 10.1007/s12185-013-1404-y. Epub 2013 Aug 11.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Complement C5 / antagonists & inhibitors
  • Female
  • Hemoglobinuria, Paroxysmal / drug therapy*
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects*
  • Immunologic Factors / therapeutic use*
  • Japan
  • Male
  • Middle Aged
  • Risk Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Complement C5
  • Immunologic Factors
  • eculizumab