Abstract
BackgroundIn 2013, eculizumab was approved for treatment of the atypical hemolytic–uremic syndrome (aHUS) in Japan, which was defined as a thrombotic microangiopathy (TMA) excluding Shiga toxin-producing Escherichia coli-HUS and thrombotic thrombocytopenic purpura. Simultaneously, post-marketing surveillance was started to assess its safety and effectiveness. In 2016, Japanese clinical guide redefined terms to limit the use of “aHUS” to complement-mediated HUS only. Accordingly, TMA with other causes was defined as secondary TMA. Here we report the interim analysis of post-marketing surveillance of pediatric patients with aHUS and secondary TMA.MethodsPediatric patients treated with eculizumab from approval to 15 March 2017 were included in this observational real-world study. Clinical endpoints of effectiveness were TMA event–free status, complete TMA response, platelet count normalization, and improvement of estimated glomerular filtration rate (eGFR). Adverse reactions to eculizumab were also analyzed.ResultsIn 27 pediatric patients with aHUS, median age at diagnosis was 4 years. Complement genes’ variants were detected in 14 of 21 patients (66.7%). Median time from diagnosis to eculizumab initiation was 2.0 days. TMA event–free status, complete TMA response, platelet normalization, and improvement in eGFR were achieved in 85.2, 36.4, 78.3, and 75.0% of patients, respectively. Three patients with aHUS died. Twenty-four and 10 adverse reactions were reported in 31 aHUS patients and 17 secondary TMA patients, respectively; however, no eculizumab-related death or meningococcal infection was reported.ConclusionsThis interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting.
Highlights
Atypical hemolytic–uremic syndrome, a thrombotic microangiopathy (TMA), is a rare disease characterized by the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury (AKI) [1, 2]
The definition of atypical hemolytic–uremic syndrome (aHUS) has changed over time in Japan; the revised guide 2015 limits the use of the term “aHUS” to complement-mediated HUS only, thereby excluding any TMA associated with transplantation, infection, drugs, autoimmune diseases, malignancies, or metabolic disorders [2]
Throughout this report, we use “aHUS” to mean complement-mediated HUS, according to the definition in the 2015 Japanese clinical guide. Both aHUS and secondary TMA are included in the present analysis, because the broader (i.e., 2013) definition of aHUS was used for diagnosis in the patient population included
Summary
Atypical hemolytic–uremic syndrome (aHUS), a thrombotic microangiopathy (TMA), is a rare disease characterized by the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury (AKI) [1, 2]. The diagnostic criteria for aHUS were defined in a Japanese clinical guide by the Japan Pediatric Society and Japanese Society of Nephrology, published in 2013 [8, 9]. The definition of aHUS has changed over time in Japan; the revised guide 2015 (published in 2016) limits the use of the term “aHUS” to complement-mediated HUS only, thereby excluding any TMA associated with transplantation, infection, drugs, autoimmune diseases, malignancies, or metabolic disorders (which is defined as “secondary TMA”) [2]. Throughout this report, we use “aHUS” to mean complement-mediated HUS, according to the definition in the 2015 Japanese clinical guide Both aHUS and secondary TMA are included in the present analysis, because the broader (i.e., 2013) definition of aHUS was used for diagnosis in the patient population included. Two-sided P values (significance level 0.05) were used in all analyses
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