Effectiveness and Safety of Switching to Ravulizumab From Eculizumab in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome: A Global aHUS Registry Analysis

Abstract

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation that may lead to kidney failure. Ravulizumab and eculizumab are complement C5 inhibitors approved for the treatment of aHUS. This study assessed the real-world effectiveness and safety of switching to ravulizumab from eculizumab in kidney transplant recipients with aHUS. Methods: The Global aHUS Registry is a multicenter study enrolling patients with aHUS since 2012. Effectiveness and safety outcomes were assessed in kidney transplant recipients with aHUS who switched to ravulizumab from eculizumab up to September 2, 2024. Results: Overall, 38 patients received a kidney transplant before ravulizumab initiation; 27 patients with ≥3 months of ravulizumab treatment were included in the patient characteristics and effectiveness analyses. Median (range) time on eculizumab and ravulizumab treatment was 66.1 (3.7, 158.3) and 24.1 (4.2, 49.3) months, respectively (n = 27); time from last kidney transplantation to ravulizumab initiation was 65.9 (3.7, 184.0) months. Following ravulizumab initiation, laboratory parameters remained stable, and no kidney transplant rejections/graft failures were reported. In the safety analysis (n = 38), 23 adverse events were reported in 19 patients (50.0%) at or after ravulizumab initiation, and none were considered treatment-related. No new events of thrombotic microangiopathy or kidney impairment and no meningococcal infections or deaths were reported. Conclusion: This analysis from the Global aHUS Registry provides real-world evidence to demonstrate that the transition to ravulizumab from eculizumab in kidney transplant recipients with aHUS is successful, with stable graft function with no treatment-related safety concerns. Trial Registration: ClinicalTrials.gov identifier: NCT01522183.