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Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan

BACKGROUND: Eculizumab was approved for atypical haemolytic uraemic syndrome (aHUS) in Japan in 2013. Post-marketing surveillance (PMS) was mandated by regulatory authorities to assess the safety and effectiveness of eculizumab in patients with aHUS in a real-world setting. METHODS: Paediatric patie...

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Autores principales: Ito, Shuichi, Hataya, Hiroshi, Ashida, Akira, Hamada, Riku, Ishikawa, Tomoaki, Ishikawa, Yumiko, Shimono, Akihiko, Konomoto, Takao, Miyazawa, Tomoki, Ogura, Masao, Tanaka, Kazuki, Kagami, Shoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923705/
https://www.ncbi.nlm.nih.gov/pubmed/35438790
http://dx.doi.org/10.1093/ndt/gfac150
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author Ito, Shuichi
Hataya, Hiroshi
Ashida, Akira
Hamada, Riku
Ishikawa, Tomoaki
Ishikawa, Yumiko
Shimono, Akihiko
Konomoto, Takao
Miyazawa, Tomoki
Ogura, Masao
Tanaka, Kazuki
Kagami, Shoji
author_facet Ito, Shuichi
Hataya, Hiroshi
Ashida, Akira
Hamada, Riku
Ishikawa, Tomoaki
Ishikawa, Yumiko
Shimono, Akihiko
Konomoto, Takao
Miyazawa, Tomoki
Ogura, Masao
Tanaka, Kazuki
Kagami, Shoji
author_sort Ito, Shuichi
collection PubMed
description BACKGROUND: Eculizumab was approved for atypical haemolytic uraemic syndrome (aHUS) in Japan in 2013. Post-marketing surveillance (PMS) was mandated by regulatory authorities to assess the safety and effectiveness of eculizumab in patients with aHUS in a real-world setting. METHODS: Paediatric patients in the PMS cohort who were <18 years of age at the first administration of eculizumab and diagnosed with aHUS [excluding Shiga toxin–producing Escherichia coli HUS, thrombotic thrombocytopaenic purpura and secondary thrombotic microangiopathy (TMA)] were included in the effectiveness and safety analysis. Clinical endpoints of effectiveness [complete TMA response, TMA event-free status, platelet (PLT) count and lactate dehydrogenase (LDH) normalization, serum creatinine (sCr) decrease and estimated glomerular filtration rate (eGFR) improvement] were analysed in patients treated with at least one dose of eculizumab. Serious adverse events (SAEs) were also evaluated. RESULTS: A total of 40 paediatric patients (median age 5 years) were included. The median eculizumab treatment duration was 66 weeks. PLT count, LDH and eGFR significantly improved at 10 days post-treatment. Complete TMA response, haematologic normalization, sCr decrease, eGFR improvement and TMA event-free status were achieved by 73.3%, 73.3%, 70.0%, 78.3% and 77.5% of patients, respectively. Discontinuation criteria were met by 18 patients: 13 patients maintained treatment discontinuation at the end of observation and 5 patients, including 1 patient with aHUS relapse, continued the treatment but extended the treatment interval. During eculizumab treatment, 59 SAEs (0.66/person-year) were reported. Although four deaths were reported, none of them were related to eculizumab. CONCLUSION: Eculizumab was well tolerated and effective for paediatric patients with aHUS in the real-world setting in Japan.
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spelling pubmed-99237052023-02-13 Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan Ito, Shuichi Hataya, Hiroshi Ashida, Akira Hamada, Riku Ishikawa, Tomoaki Ishikawa, Yumiko Shimono, Akihiko Konomoto, Takao Miyazawa, Tomoki Ogura, Masao Tanaka, Kazuki Kagami, Shoji Nephrol Dial Transplant Original Article BACKGROUND: Eculizumab was approved for atypical haemolytic uraemic syndrome (aHUS) in Japan in 2013. Post-marketing surveillance (PMS) was mandated by regulatory authorities to assess the safety and effectiveness of eculizumab in patients with aHUS in a real-world setting. METHODS: Paediatric patients in the PMS cohort who were <18 years of age at the first administration of eculizumab and diagnosed with aHUS [excluding Shiga toxin–producing Escherichia coli HUS, thrombotic thrombocytopaenic purpura and secondary thrombotic microangiopathy (TMA)] were included in the effectiveness and safety analysis. Clinical endpoints of effectiveness [complete TMA response, TMA event-free status, platelet (PLT) count and lactate dehydrogenase (LDH) normalization, serum creatinine (sCr) decrease and estimated glomerular filtration rate (eGFR) improvement] were analysed in patients treated with at least one dose of eculizumab. Serious adverse events (SAEs) were also evaluated. RESULTS: A total of 40 paediatric patients (median age 5 years) were included. The median eculizumab treatment duration was 66 weeks. PLT count, LDH and eGFR significantly improved at 10 days post-treatment. Complete TMA response, haematologic normalization, sCr decrease, eGFR improvement and TMA event-free status were achieved by 73.3%, 73.3%, 70.0%, 78.3% and 77.5% of patients, respectively. Discontinuation criteria were met by 18 patients: 13 patients maintained treatment discontinuation at the end of observation and 5 patients, including 1 patient with aHUS relapse, continued the treatment but extended the treatment interval. During eculizumab treatment, 59 SAEs (0.66/person-year) were reported. Although four deaths were reported, none of them were related to eculizumab. CONCLUSION: Eculizumab was well tolerated and effective for paediatric patients with aHUS in the real-world setting in Japan. Oxford University Press 2022-04-19 /pmc/articles/PMC9923705/ /pubmed/35438790 http://dx.doi.org/10.1093/ndt/gfac150 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Ito, Shuichi
Hataya, Hiroshi
Ashida, Akira
Hamada, Riku
Ishikawa, Tomoaki
Ishikawa, Yumiko
Shimono, Akihiko
Konomoto, Takao
Miyazawa, Tomoki
Ogura, Masao
Tanaka, Kazuki
Kagami, Shoji
Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan
title Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan
title_full Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan
title_fullStr Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan
title_full_unstemmed Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan
title_short Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan
title_sort eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in japan
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923705/
https://www.ncbi.nlm.nih.gov/pubmed/35438790
http://dx.doi.org/10.1093/ndt/gfac150
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