#3423 Efficacy and safety of ravulizumab for the maintenance of aHUS remission after kidney transplant

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) triggered by complement dysregulation. Ravulizumab, a next generation complement inhibitor provides immediate and sustained complement C5 inhibition. The aim of this study was to assess clinical efficacy, safety and tolerability of ravulizumab in aHUS patients. Method Patients with a clinical diagnosis of aHUS treated with eculizumab for at least three months were switched to ravulizumab. The first ravulizumab infusion was administered at least two weeks after the last eculizumab dose, followed by a second infusion two weeks later and subsequent doses every eight weeks. Results Four patients with end-stage renal disease due to aHUS had previously undergone kidney transplant. At the time of switching to ravulizumab, none required dialysis, and no new dialysis events occurred during treatment. Estimated glomerular filtration rate (eGFR), platelet count, lactate dehydrogenase (LDH), creatinine, haptoglobin and hemoglobin levels remained stable throughout the study. No clinical signs of TMA or adverse event (AE) relapses were reported. Genetic testing confirmed at least one aHUS associated variant in the complement system in all patients. No meningococcal infections were reported during the study. Conclusion Long-term treatment with ravulizumab proved to be well tolerated and associated with sustained hematologic and renal parameters, and improved quality of life. Furthermore, the close attention to vaccinations status and preventive antibiotic therapy ensured no meningococcal infections during the treatment. Decision which patients required lifelong treatment involved consideration of a wide range of factors. Our study provides compelling evidence on the complexity of safety aspects of ravulizumab treatment.