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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)406-416
Number of pages11
JournalInternational Journal of Hematology
Volume98
Issue number4
DOIs
Publication statusPublished - 2013 Oct

Fingerprint

Paroxysmal Hemoglobinuria
Safety
Hemolysis
Quality of Life
Kidney
Erythrocyte Transfusion
Complement Activation
Thromboembolism
Hematopoietic Stem Cells
eculizumab
Dyspnea
Fatigue
Thrombosis
Therapeutics
Bone Marrow
Monoclonal Antibodies
Mortality
Infection

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Long-term efficacy and safety of eculizumab in Japanese patients with PNH : AEGIS trial. / Kanakura, Yuzuru; Ohyashiki, Kazuma; Shichishima, Tsutomu; Okamoto, Shinichiro; Ando, Kiyoshi; Ninomiya, Haruhiko; Kawaguchi, Tatsuya; Nakao, Shinji; Nakakuma, Hideki; Nishimura, Jun Ichi; Kinoshita, Taroh; Bedrosian, Camille L.; Ozawa, Keiya; Omine, Mitsuhiro.

In: International Journal of Hematology, Vol. 98, No. 4, 10.2013, p. 406-416.

Research output: Contribution to journalArticle

Kanakura, Y, Ohyashiki, K, Shichishima, T, Okamoto, S, Ando, K, Ninomiya, H, Kawaguchi, T, Nakao, S, Nakakuma, H, Nishimura, JI, Kinoshita, T, Bedrosian, CL, Ozawa, K & Omine, M 2013, 'Long-term efficacy and safety of eculizumab in Japanese patients with PNH: AEGIS trial', International Journal of Hematology, vol. 98, no. 4, pp. 406-416. https://doi.org/10.1007/s12185-013-1404-y
Kanakura, Yuzuru ; Ohyashiki, Kazuma ; Shichishima, Tsutomu ; Okamoto, Shinichiro ; Ando, Kiyoshi ; Ninomiya, Haruhiko ; Kawaguchi, Tatsuya ; Nakao, Shinji ; Nakakuma, Hideki ; Nishimura, Jun Ichi ; Kinoshita, Taroh ; Bedrosian, Camille L. ; Ozawa, Keiya ; Omine, Mitsuhiro. / Long-term efficacy and safety of eculizumab in Japanese patients with PNH : AEGIS trial. In: International Journal of Hematology. 2013 ; Vol. 98, No. 4. pp. 406-416.
@article{671ef79642f747bc9f162f620fe302b3,
title = "Long-term efficacy and safety of eculizumab in Japanese patients with PNH: AEGIS trial",
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 = "Complement-inactivating agents, Eculizumab, Hematopoietic stem cell, Hemolysis, Paroxysmal nocturnal hemoglobinuria",
author = "Yuzuru Kanakura and Kazuma Ohyashiki and Tsutomu Shichishima and Shinichiro Okamoto and Kiyoshi Ando and Haruhiko Ninomiya and Tatsuya Kawaguchi and Shinji Nakao and Hideki Nakakuma and Nishimura, {Jun Ichi} and Taroh Kinoshita and Bedrosian, {Camille L.} and Keiya Ozawa and Mitsuhiro Omine",
year = "2013",
month = "10",
doi = "10.1007/s12185-013-1404-y",
language = "English",
volume = "98",
pages = "406--416",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",
number = "4",

}

TY - JOUR

T1 - Long-term efficacy and safety of eculizumab in Japanese patients with PNH

T2 - AEGIS trial

AU - Kanakura, Yuzuru

AU - Ohyashiki, Kazuma

AU - Shichishima, Tsutomu

AU - Okamoto, Shinichiro

AU - Ando, Kiyoshi

AU - Ninomiya, Haruhiko

AU - Kawaguchi, Tatsuya

AU - Nakao, Shinji

AU - Nakakuma, Hideki

AU - Nishimura, Jun Ichi

AU - Kinoshita, Taroh

AU - Bedrosian, Camille L.

AU - Ozawa, Keiya

AU - Omine, Mitsuhiro

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - Complement-inactivating agents

KW - Eculizumab

KW - Hematopoietic stem cell

KW - Hemolysis

KW - Paroxysmal nocturnal hemoglobinuria

UR - http://www.scopus.com/inward/record.url?scp=84886803820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886803820&partnerID=8YFLogxK

U2 - 10.1007/s12185-013-1404-y

DO - 10.1007/s12185-013-1404-y

M3 - Article

VL - 98

SP - 406

EP - 416

JO - International Journal of Hematology

JF - International Journal of Hematology

SN - 0925-5710

IS - 4

ER -