PMID- 37515657
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231023
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 118
IP  - 4
DP  - 2023 Oct
TI  - Real-world safety profile of eculizumab in patients with paroxysmal nocturnal 
      hemoglobinuria, atypical hemolytic uremic syndrome, or generalized myasthenia 
      gravis: an integrated analysis of post-marketing surveillance in Japan.
PG  - 419-431
LID - 10.1007/s12185-023-03630-x [doi]
AB  - Eculizumab is a C5 inhibitor approved for the treatment of paroxysmal nocturnal 
      hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and 
      anti-acetylcholine receptor antibody-positive generalized myasthenia gravis 
      (AChR + gMG) in Japan. We report integrated safety data from post-marketing 
      surveillance in these three indications, focusing on commonly occurring adverse 
      events (AEs) and infection-related AEs. Of 1219 patients registered, 1055 (PNH: 
      780; aHUS: 192; AChR + gMG: 83) had available safety data. Total eculizumab 
      exposure was 3977.361 patient-years. AEs were reported in 74.03% of patients. AEs 
      with an incidence of  >/= 1.0 per 100 patient-years included hemolysis, headache, 
      nasopharyngitis, renal impairment, anemia, pneumonia, upper respiratory tract 
      inflammation, influenza, condition aggravated, and infection. The incidence of 
      infection-related AEs was 21.30 per 100 patient-years, the most frequent types 
      (>/= 1.0 per 100 patient-years) being nasopharyngitis, pneumonia, influenza, and 
      infection. Meningococcal infections were reported in four patients (0.10 per 100 
      patient-years). Two patients died from meningococcal sepsis, with a mortality 
      rate of 0.05 per 100 patient-years. This is the largest safety dataset on 
      eculizumab in Japan derived from more than 10 years of clinical experience. No 
      new safety signals were observed and the safety profile of eculizumab was 
      consistent with that in previous clinical trials and international real-world 
      safety analyses.
CI  - (c) 2023. Japanese Society of Hematology.
FAU - Nishimura, Jun-Ichi
AU  - Nishimura JI
AD  - Department of Hematology and Oncology, Osaka University Graduate School of 
      Medicine, Suita, Japan. junnishi@bldon.med.osaka-u.ac.jp.
FAU - Kawaguchi, Tatsuya
AU  - Kawaguchi T
AD  - Department of Medical Technology, Kumamoto Health Science University, Kumamoto, 
      Japan.
FAU - Ito, Shuichi
AU  - Ito S
AD  - Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 
      Yokohama, Japan.
FAU - Murai, Hiroyuki
AU  - Murai H
AD  - Department of Neurology, International University of Health and Welfare, Narita, 
      Japan.
FAU - Shimono, Akihiko
AU  - Shimono A
AD  - Alexion Pharma GK, Tokyo, Japan.
FAU - Matsuda, Takahisa
AU  - Matsuda T
AD  - Alexion Pharma GK, Tokyo, Japan.
FAU - Fukamizu, Yuji
AU  - Fukamizu Y
AD  - Alexion Pharma GK, Tokyo, Japan.
FAU - Akiyama, Hirozumi
AU  - Akiyama H
AD  - Alexion Pharma GK, Tokyo, Japan.
FAU - Hayashi, Hideo
AU  - Hayashi H
AD  - Alexion Pharma GK, Tokyo, Japan.
FAU - Nakano, Takashi
AU  - Nakano T
AD  - Department of Pediatrics, Kawasaki Medical School, Okayama, Japan.
FAU - Maruyama, Shoichi
AU  - Maruyama S
AD  - Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20230729
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - A3ULP0F556 (eculizumab)
RN  - 0 (Complement Inactivating Agents)
SB  - IM
MH  - Humans
MH  - *Atypical Hemolytic Uremic Syndrome/drug therapy/chemically induced
MH  - *Hemoglobinuria, Paroxysmal/drug therapy
MH  - Japan/epidemiology
MH  - *Influenza, Human/chemically induced/drug therapy
MH  - *Nasopharyngitis/chemically induced/drug therapy
MH  - Complement Inactivating Agents/adverse effects
MH  - *Myasthenia Gravis/drug therapy/chemically induced
MH  - Product Surveillance, Postmarketing
MH  - *Pneumonia
OTO - NOTNLM
OT  - Atypical hemolytic uremic syndrome
OT  - Eculizumab
OT  - Generalized myasthenia gravis
OT  - Paroxysmal nocturnal hemoglobinuria
OT  - Post-marketing surveillance
EDAT- 2023/07/29 21:46
MHDA- 2023/10/23 12:42
CRDT- 2023/07/29 11:06
PHST- 2023/04/14 00:00 [received]
PHST- 2023/06/20 00:00 [accepted]
PHST- 2023/06/19 00:00 [revised]
PHST- 2023/10/23 12:42 [medline]
PHST- 2023/07/29 21:46 [pubmed]
PHST- 2023/07/29 11:06 [entrez]
AID - 10.1007/s12185-023-03630-x [pii]
AID - 10.1007/s12185-023-03630-x [doi]
PST - ppublish
SO  - Int J Hematol. 2023 Oct;118(4):419-431. doi: 10.1007/s12185-023-03630-x. Epub 
      2023 Jul 29.