The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review

Background The atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy associated with high morbidity and high mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, was the first medication approved for treating aHUS in 2011. Objective The objective of this study is to evaluate the efficacy and safety of eculizumab treatment in pediatric patients with aHUS. Data sources We consulted PubMed, Scopus, SciELO, and Cochrane Library databases in July 2021. The descriptors were as follows: “Atypical Hemolytic Uremic Syndrome,” “aHUS,” “eculizumab,” “Pediatrics,” “Pediatric,” “Child,” “Children,” “Adolescent.” Study eligibility criteria The study eligibility criteria are as follows: clinical trials and observational studies that included pediatric patients with aHUS diagnosis and who were treated with eculizumab. Participants and interventions The participants are pediatric patients, up to 18 years old, with aHUS. The intervention was eculizumab treatment. Study appraisal For quality assessment, we used the Newcastle–Ottawa Scale, the National Institutes of Health (NIH) quality assessment tool for case series studies, and the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Results The initial search retrieved 433 studies, from which 15 were selected after complete assessment: 9 cohorts, 4 case series, and 1 clinical trial. The publication date ranged from 2015 to 2021. In total, 940 pediatric patients were included, and 682 received eculizumab. All studies reported improvements in renal and hematological parameters in most of the patients treated with eculizumab. The mortality rate was 1.6% for all patients treated with eculizumab. Limitations The number of studies is limited, and the included studies were methodologically heterogeneous. The studies were mostly observational and many had small sample sizes. Conclusions Eculizumab appears to be safe and effective for the treatment of aHUS in pediatric patients. More research is necessary to establish long-term efficacy, safety, and time of discontinuation. Systematic review registration number CRD42021266255.