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; Kubo, Shoji

doi:10.1093/ndt/gfac150

Cited by 7 publications

(1 citation statement)

References 39 publications

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“…A haematologic normalization was defined as platelet count normalization (≥150 × 10 9 /L) and LDH normalization (˂1.5 times the age-matched upper limit of normal). Each normalization should be maintained for ≥4 weeks [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Immunosuppressive Therapy of Antibody-Mediated aHUS and TTP

Kelen,

Horváth,

Kis

et al. 2023

IJMS

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The recent classification of pediatric thrombotic microangiopathies (TMA) takes into consideration mechanisms of disease for guidance to targeted therapies. We present our experience with seven patients with antibody mediated atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). Five children had aHUS with antibodies against complement factor H (CFH-ab) and two with TTP with antibodies against metalloproteinase ADAMTS13. In the aHUS cases diagnosed and treated before the eculizumab era, CFH-ab was detected using the ELISA assay. Mutational analysis of selected complement genes was performed. TTP was diagnosed if, in addition to microangiopathic hemolytic anemia and thrombocytopenia, ischemic organ involvement and severe deficiency in ADAMTS13 activity were present. Treatment protocol consisted of plasma exchanges (PE) and steroid pulses, followed by the combination of cyclophosphamide and rituximab to achieve long-term immunosuppression. Four patients with CFH-ab and the TTP patients with ADAMTS13 antibodies came into sustained remission. After a median follow-up of 11.7 (range 7.7–12.9) years without maintenance therapy, no disease recurrence was observed; nevertheless, six patients, two had hypertension and two had proteinuria as a late consequence. One patient, with late diagnosis of CFH-ab and additional genetic risk factors who was treated only with PE and plasma substitution, reached end-stage renal disease and was later successfully transplanted using eculizumab prophylaxis. In the cases of antibody-mediated TMAs, PE and early immunosuppressive treatment may result in sustained remission with preserved kidney function. Further data are needed to establish optimal treatment of anti-FH antibody-associated HUS.

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Section: Methodsmentioning

confidence: 99%