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Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance

BACKGROUND: Eculizumab has been available for the treatment of atypical hemolytic–uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by J...

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Autores principales: Kato, Hideki, Miyakawa, Yoshitaka, Hidaka, Yoshihiko, Inoue, Norimitsu, Ito, Shuichi, Kagami, Shoji, Kaname, Shinya, Matsumoto, Masanori, Mizuno, Masashi, Matsuda, Takahisa, Shimono, Akihiko, Maruyama, Shoichi, Fujimura, Yoshihiro, Nangaku, Masaomi, Okada, Hirokazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344388/
https://www.ncbi.nlm.nih.gov/pubmed/29959568
http://dx.doi.org/10.1007/s10157-018-1609-8
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author Kato, Hideki
Miyakawa, Yoshitaka
Hidaka, Yoshihiko
Inoue, Norimitsu
Ito, Shuichi
Kagami, Shoji
Kaname, Shinya
Matsumoto, Masanori
Mizuno, Masashi
Matsuda, Takahisa
Shimono, Akihiko
Maruyama, Shoichi
Fujimura, Yoshihiro
Nangaku, Masaomi
Okada, Hirokazu
author_facet Kato, Hideki
Miyakawa, Yoshitaka
Hidaka, Yoshihiko
Inoue, Norimitsu
Ito, Shuichi
Kagami, Shoji
Kaname, Shinya
Matsumoto, Masanori
Mizuno, Masashi
Matsuda, Takahisa
Shimono, Akihiko
Maruyama, Shoichi
Fujimura, Yoshihiro
Nangaku, Masaomi
Okada, Hirokazu
author_sort Kato, Hideki
collection PubMed
description BACKGROUND: Eculizumab has been available for the treatment of atypical hemolytic–uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations. METHODS: This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based on Japanese clinical guide published in 2013 as inclusion criteria and treated with eculizumab. Although the term aHUS was redefined to denote only complement-mediated HUS in the guide revised in 2016, the patients with TMA caused by other causes (secondary TMA) were included. Patient outcomes and safety were evaluated at 6 months, 12 months, and annually thereafter. RESULTS: Thirty-three patients with aHUS and 27 patients with secondary TMA were enrolled. Median treatment duration of aHUS was 24weeks. Complement genes variants were detected in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine (SCr) improved within 1-month after eculizumab initiation. TMA event-free status, complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9% (19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients, respectively. Thirty-three and 11 adverse reactions were observed in patients with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively. CONCLUSIONS: This interim analysis confirmed the acceptable safety profile and effectiveness of eculizumab for Japanese adult aHUS patients in real-world settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10157-018-1609-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-63443882019-02-08 Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance Kato, Hideki Miyakawa, Yoshitaka Hidaka, Yoshihiko Inoue, Norimitsu Ito, Shuichi Kagami, Shoji Kaname, Shinya Matsumoto, Masanori Mizuno, Masashi Matsuda, Takahisa Shimono, Akihiko Maruyama, Shoichi Fujimura, Yoshihiro Nangaku, Masaomi Okada, Hirokazu Clin Exp Nephrol Original Article BACKGROUND: Eculizumab has been available for the treatment of atypical hemolytic–uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations. METHODS: This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based on Japanese clinical guide published in 2013 as inclusion criteria and treated with eculizumab. Although the term aHUS was redefined to denote only complement-mediated HUS in the guide revised in 2016, the patients with TMA caused by other causes (secondary TMA) were included. Patient outcomes and safety were evaluated at 6 months, 12 months, and annually thereafter. RESULTS: Thirty-three patients with aHUS and 27 patients with secondary TMA were enrolled. Median treatment duration of aHUS was 24weeks. Complement genes variants were detected in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine (SCr) improved within 1-month after eculizumab initiation. TMA event-free status, complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9% (19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients, respectively. Thirty-three and 11 adverse reactions were observed in patients with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively. CONCLUSIONS: This interim analysis confirmed the acceptable safety profile and effectiveness of eculizumab for Japanese adult aHUS patients in real-world settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10157-018-1609-8) contains supplementary material, which is available to authorized users. Springer Singapore 2018-06-29 2019 /pmc/articles/PMC6344388/ /pubmed/29959568 http://dx.doi.org/10.1007/s10157-018-1609-8 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Kato, Hideki
Miyakawa, Yoshitaka
Hidaka, Yoshihiko
Inoue, Norimitsu
Ito, Shuichi
Kagami, Shoji
Kaname, Shinya
Matsumoto, Masanori
Mizuno, Masashi
Matsuda, Takahisa
Shimono, Akihiko
Maruyama, Shoichi
Fujimura, Yoshihiro
Nangaku, Masaomi
Okada, Hirokazu
Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance
title Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance
title_full Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance
title_fullStr Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance
title_full_unstemmed Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance
title_short Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance
title_sort safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in japan: interim analysis of post-marketing surveillance
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344388/
https://www.ncbi.nlm.nih.gov/pubmed/29959568
http://dx.doi.org/10.1007/s10157-018-1609-8
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