Background: Atypical Haemolytic Uremic Syndrome (aHUS) is a rare but life-threatening thrombotic microangiopathy. If inadequately managed, aHUS can lead to progressive kidney failure, cardiovascular complications and multiorgan dysfunction, resulting in high healthcare costs and a substantial impact on patients' quality of life. Novel complement inhibitors offer potential advantages, yet comprehensive evidence comparing their efficacy and safety is limited. This protocol elaborates the systematic review plans to evaluate the effectiveness and the drug safety of complement inhibitors in aHUS.

Methods: A systematic search will be conducted across PubMed, Embase, Cochrane Library, Web of Science and Scopus to identify relevant studies. Eligible studies include randomised controlled trials (RCTs), observational studies and case series with at least three aHUS patients treated with novel complement inhibitors. Two independent reviewers will perform data extraction and quality assessment using standardised tools, including the Risk of Bias Tool 2 for RCTs and the Newcastle-Ottawa Scale for observational studies. A meta-analysis will be conducted if feasible, utilising a random-effects model to account for study heterogeneity. Background: Ethical approval is not required as only previously published data will be used. Results will be disseminated via peer-reviewed journals and conferences, targeting healthcare professionals and policymakers to support evidence-based decision-making in aHUS management. CRD42025629879.