Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan. Issue 2 (19th April 2022)

• Record Type: Journal Article
• Authors: Ito, Shuichi; Hataya, Hiroshi; Ashida, Akira; Hamada, Riku; Ishikawa, Tomoaki; Ishikawa, Yumiko; Shimono, Akihiko; Konomoto, Takao; Miyazawa, Tomoki; Ogura, Masao; Tanaka, Kazuki; Kagami, Shoji
• Is Part Of: Nephrology dialysis transplantation. Volume 38:Issue 2(2023)
• Page Start: 414
• Page End: 424
• Publication Date: 2022-04-19
• Subjects: atypical haemolytic uraemic syndrome -- complement -- eculizumab -- post-marketing surveillance -- thrombotic microangiopathy; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfac150
• Languages: English
• ISSNs: 0931-0509

Abstract

ABSTRACT: 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. Graphical Abstract: