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

Abstract

Background In 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. Methods Pediatric 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. Results In 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. Conclusions This interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting.

The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab

“…The complement protein C5 inhibitor eculizumab (Soliris®, Alexion Pharmaceuticals, Inc., Boston, MA, United States) has been shown to be efficacious and safe in treating aHUS in adults and children over the last decade, both in clinical trials and real-world settings [6][7][8][9][10][11][12][13]. However, despite its proven effectiveness, intravenous (IV) eculizumab infusions are required once every 2 weeks, which may be burdensome for patients and caregivers.…”

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies

“…After excluding clearly irrelevant studies (i.e., pre-clinical studies and clinical trials with no evaluation of the eligible outcomes, other observational studies that did not meet the conditions to be considered as real-life NRSI, such as case series or case reports), 28 pharmaceutical industry-sponsored clinical trials corresponding to phases 1 to 3 evaluation of various complement inhibitors, and 15 real-life NRSI reflecting uses of these medicines in real-world settings were found to be eligible: these studies assess outcomes in PNH (No. of clinical trials/real-life NRSI: 7/7), aHUS (7/8), rgMG (3/0), aAMR (6/0), and DGF (5/0), and included a total population of 7484 participants [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ,…”

Eculizumab in paediatric atypical haemolytic uraemic syndrome: Lessons learned from a single‐centre experience in the United Arab Emirates

“…Our data also echo a more recent interim analysis of a post-marketing surveillance from Japan, where the authors showed that over three quarters of paediatric patients achieved TMA and renal responses, and therapy was well-tolerated. 12 Conclusion aHUS can be a debilitating disease in growing children as it is associated with serious morbidity and mortality. Prompt patient diagnosis and early introduction of therapy remain key for effective disease control and favourable prognosis.…”