Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan

Naoko Ito, Hiroshi Hataya, Ken Saida, Yoshiro Amano, Yoshihiko Hidaka, Yaeko Motoyoshi, Toshiyuki Ohta, Yasuhiro Yoshida, Chikako Terano, Tadashi Iwasa, Wataru Kubota, Hidetoshi Takada, Toshiro Hara, Yoshihiro Fujimura, Shuichi Ito

Research output: Contribution to journalArticle

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Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease with frequent progression to end-stage renal disease (ESRD). Eculizumab, a humanized anti-C5 monoclonal antibody targeting the activated complement pathway, has recently been introduced as a novel therapy against aHUS. We, therefore, investigated the efficacy and safety of eculizumab in Japanese pediatric patients. Methods: We retrospectively analyzed clinical course and laboratory data of the first ten children with aHUS treated with eculizumab nationwide. Results: Seven patients were resistant to plasma therapy and three were dependent on it. Causative gene mutations were found in five patients. Two patients had anti-complement factor H autoantibody. Three patients had a family history of thrombotic microangiopathy (TMA). After initiation of eculizumab, all patients immediately achieved hematological remission and could successfully discontinue plasma therapy. The median periods to normalization of platelet count, lactate dehydrogenase levels and disappearance of schistocytes were 5.5, 17 and 12 days, respectively. Nine patients recovered their renal function and the median period to terminate renal replacement therapy (RRT) was 3 days. However, two patients progressed to ESRD and required chronic RRT at the last observation. No patients had a relapse of TMA under regular eculizumab therapy. No serious adverse events occurred during the follow-up period. Conclusions: Eculizumab is efficacious and well-tolerated therapy for children with aHUS. Although pathogenic mutations could not be detected in five patients, all patients showed immediate normalization of hematological abnormalities, strongly suggesting complement-related aHUS. This prompt hematological amelioration can become an indicator for therapeutic efficacy of eculizumab. However, appropriate indications and optimal duration of the treatment remain unclear.

Original languageEnglish
Pages (from-to)265-272
Number of pages8
JournalClinical and Experimental Nephrology
Volume20
Issue number2
DOIs
Publication statusPublished - Apr 1 2016

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Japan
Safety
Thrombotic Microangiopathies
Renal Replacement Therapy
Therapeutics
Chronic Kidney Failure
Atypical Hemolytic Uremic Syndrome
eculizumab
Complement Factor H
Mutation
Platelet Count
L-Lactate Dehydrogenase
Autoantibodies
Monoclonal Antibodies
Observation
Pediatrics
Kidney
Recurrence
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan. / Ito, Naoko; Hataya, Hiroshi; Saida, Ken; Amano, Yoshiro; Hidaka, Yoshihiko; Motoyoshi, Yaeko; Ohta, Toshiyuki; Yoshida, Yasuhiro; Terano, Chikako; Iwasa, Tadashi; Kubota, Wataru; Takada, Hidetoshi; Hara, Toshiro; Fujimura, Yoshihiro; Ito, Shuichi.

In: Clinical and Experimental Nephrology, Vol. 20, No. 2, 01.04.2016, p. 265-272.

Research output: Contribution to journalArticle

Ito, N, Hataya, H, Saida, K, Amano, Y, Hidaka, Y, Motoyoshi, Y, Ohta, T, Yoshida, Y, Terano, C, Iwasa, T, Kubota, W, Takada, H, Hara, T, Fujimura, Y & Ito, S 2016, 'Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan', Clinical and Experimental Nephrology, vol. 20, no. 2, pp. 265-272. https://doi.org/10.1007/s10157-015-1142-y
Ito, Naoko ; Hataya, Hiroshi ; Saida, Ken ; Amano, Yoshiro ; Hidaka, Yoshihiko ; Motoyoshi, Yaeko ; Ohta, Toshiyuki ; Yoshida, Yasuhiro ; Terano, Chikako ; Iwasa, Tadashi ; Kubota, Wataru ; Takada, Hidetoshi ; Hara, Toshiro ; Fujimura, Yoshihiro ; Ito, Shuichi. / Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan. In: Clinical and Experimental Nephrology. 2016 ; Vol. 20, No. 2. pp. 265-272.
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AU - Ito, Naoko

AU - Hataya, Hiroshi

AU - Saida, Ken

AU - Amano, Yoshiro

AU - Hidaka, Yoshihiko

AU - Motoyoshi, Yaeko

AU - Ohta, Toshiyuki

AU - Yoshida, Yasuhiro

AU - Terano, Chikako

AU - Iwasa, Tadashi

AU - Kubota, Wataru

AU - Takada, Hidetoshi

AU - Hara, Toshiro

AU - Fujimura, Yoshihiro

AU - Ito, Shuichi

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background: Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease with frequent progression to end-stage renal disease (ESRD). Eculizumab, a humanized anti-C5 monoclonal antibody targeting the activated complement pathway, has recently been introduced as a novel therapy against aHUS. We, therefore, investigated the efficacy and safety of eculizumab in Japanese pediatric patients. Methods: We retrospectively analyzed clinical course and laboratory data of the first ten children with aHUS treated with eculizumab nationwide. Results: Seven patients were resistant to plasma therapy and three were dependent on it. Causative gene mutations were found in five patients. Two patients had anti-complement factor H autoantibody. Three patients had a family history of thrombotic microangiopathy (TMA). After initiation of eculizumab, all patients immediately achieved hematological remission and could successfully discontinue plasma therapy. The median periods to normalization of platelet count, lactate dehydrogenase levels and disappearance of schistocytes were 5.5, 17 and 12 days, respectively. Nine patients recovered their renal function and the median period to terminate renal replacement therapy (RRT) was 3 days. However, two patients progressed to ESRD and required chronic RRT at the last observation. No patients had a relapse of TMA under regular eculizumab therapy. No serious adverse events occurred during the follow-up period. Conclusions: Eculizumab is efficacious and well-tolerated therapy for children with aHUS. Although pathogenic mutations could not be detected in five patients, all patients showed immediate normalization of hematological abnormalities, strongly suggesting complement-related aHUS. This prompt hematological amelioration can become an indicator for therapeutic efficacy of eculizumab. However, appropriate indications and optimal duration of the treatment remain unclear.

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