#243 Characteristics and safety in patients with atypical haemolytic uraemic syndrome switching to ravulizumab from eculizumab: a global registry analysis

Abstract Background and Aims Atypical haemolytic uraemic syndrome (aHUS) is a progressive rare disease caused by complement dysregulation that can result in severe organ damage and death. Ravulizumab, a next-generation terminal complement inhibitor, was designed via targeted modification of eculizumab to enhance antibody recycling and attenuate target-mediated drug disposition to achieve an extended half-life. Ravulizumab was first approved for the treatment of aHUS in 2019. Real-world evidence with ravulizumab in patients with aHUS is limited. This analysis aimed to assess real-world safety outcomes in patients with aHUS who switched to ravulizumab from eculizumab using data from the Global aHUS Registry. Method The Global aHUS Registry is a multicentre study (NCT01522183) collecting retrospective and prospective data on patients with aHUS since 2012, making it the largest registry of real-world data for this patient population. Safety outcomes (including serious and non-serious adverse events [AEs], meningococcal infections and deaths) were assessed in patients with aHUS who switched to ravulizumab from eculizumab up to 3 July 2023. Results Overall, 60 patients were included in the analysis population and evaluated for baseline demographics and characteristics, and safety outcomes. Most patients were female (70%) and the median (range) age at ravulizumab initiation was 34 (2–72) years (Table 1). In total, 27 patients (45%) had pathogenic complement variants and 19 (32%) had a kidney transplantation prior to ravulizumab initiation. Among extrarenal manifestations (experienced at any time during observation), the most common were gastrointestinal (n = 29 [48%]), central nervous system (n = 19 [32%]) and cardiovascular (n = 15 [25%]). The median (range) time on treatment was 21 (2–40) months for ravulizumab and 62 (11–155) months for eculizumab. No new events of thrombotic microangiopathy, dialysis or kidney transplantation were reported during ravulizumab treatment. One patient who was on chronic dialysis under eculizumab switched to ravulizumab; the patient returned to eculizumab (per local guidelines) for a planned kidney transplantation with the intention to switch back to ravulizumab post-transplantation (data not yet available). In total, 20 AEs were reported in 13 patients, of which none were unexpected (Table 2). Three serious AEs were reported in three patients (1 event each of squamous cell carcinoma, atrial fibrillation, SARS-CoV-2 infection). Ten AEs occurred in eight patients who received a kidney transplantation before ravulizumab initiation. Treatment-related AEs occurred in two patients while on ravulizumab: one infusion reaction event in one patient was assessed to be probably related to ravulizumab by the investigator (the event resolved within 24 hours and the patient continued treatment); one patient experienced headaches and fatigue while on ravulizumab, which resolved after switching back to eculizumab. The most common AEs were infection (n = 7 events), including SARS-CoV-2 infection (n = 4), influenza (n = 1), infection without focus (n = 1) and pulmonary nodular infiltration (n = 1); all infections were resolved except for one event of SARS-CoV-2 infection that was ongoing/persistent. No meningococcal infections or deaths were reported during ravulizumab treatment. Conclusion This analysis from the Global aHUS Registry reports the largest real-world safety dataset from patients with aHUS treated with ravulizumab. No unexpected AEs, meningococcal infections or deaths were reported during ravulizumab treatment. These data provide evidence for the long-term safety of ravulizumab in patients with aHUS who switched from eculizumab and reinforce the positive benefit–risk profile of ravulizumab.