title: Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan.
abstract: Data characterizing the safety and effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) are limited. We describe the safety and effectiveness of eculizumab in PNH patients enrolled in a post-marketing surveillance study. Types and frequencies of observed adverse events were similar to those reported in previous clinical trials and no meningococcal infection was reported. Effectiveness outcomes included the reduction of intravascular hemolysis, the change in hemoglobin (Hb) level, the withdrawal of transfusion and corticosteroids, the change of renal function, and overall survival. The effect of eculizumab on intravascular hemolysis was demonstrated by a reduction in lactate dehydrogenase levels at all measurements after baseline. Significant increases in Hb levels from baseline were also observed after 1 month's treatment with eculizumab (p < 0.01). Of those who were transfusion-dependent at baseline, the median number of transfusions decreased significantly from 18 to 0 unit/year after 1 year of treatment with eculizumab (p < 0.001). An increase in Hb and a high rate of transfusion independence were observed, especially in patients with platelet count ≥150 × 109/L. Approximately 97 % of patients showed maintenance or improvement of renal function. Overall survival rate was about 90 % (median follow-up 1.9 years). These results suggest an acceptable safety profile and favorable prognosis after eculizumab intervention.
authors.affiliation: Department of Medical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. ninomiya.haruhiko.ft@u.tsukuba.ac.jp.|Japan PNH Study Group, Tokyo, Japan. ninomiya.haruhiko.ft@u.tsukuba.ac.jp.
authors.forename: Haruhiko
authors.identifier: http://orcid.org/0000-0002-5431-7447
authors.initials: H
authors.lastname: Ninomiya
authors.affiliation: Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Obara
authors.affiliation: Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Usuki
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine, Jikei University Kashiwa Hospital, Kashiwa, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Kaichi
authors.initials: K
authors.lastname: Nishiwaki
authors.affiliation: Division of Hematology, Kinki University, Osakasayama, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Matsumura
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shichishima
authors.affiliation: Division of Hematology, Department of Internal Medicine, Keio University, Tokyo, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Department of Hematology and Oncology, Osaka University, Suita, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Nishimura
authors.affiliation: Department of Hematology, Tokyo Medical University, Tokyo, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.affiliation: Hematology/Respiratory Medicine, Kanazawa University, Kanazawa, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
authors.affiliation: Division of Hematology and Oncology, Tokai University, Isehara, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Division of Hematology, Jichi Medical University, Shimotsuke, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Departments of Hematology and Infectious Diseases, Kumamoto University, Kumamoto, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Kagoshima Tokushukai Hospital, Kagoshima, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakakuma
authors.affiliation: Alexion Pharma G.K., Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Harada
authors.affiliation: Alexion Pharma G.K., Tokyo, Japan.
authors.forename: Hirozumi
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Department of Hematology, Showa University Fujigaoka Hospital, Yokohama, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Omine
authors.affiliation: Department of Hematology and Oncology, Osaka University, Suita, Japan.|Japan PNH Study Group, Tokyo, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D006454:Hemoglobins / Q000032:analysis; D006457:Hemoglobinuria, Paroxysmal / Q000188:drug therapy*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007564:Japan; D007668:Kidney / Q000502:physiology; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; C481642:eculizumab
keywords: Eculizumab; Effectiveness; Paroxysmal nocturnal hemoglobinuria; Post-marketing surveillance; Safety