Evaluation of Ravulizumab Trough Levels in Pediatric Atypical Hemolytic Uremic Syndrome at Remission

Background: Ravulizumab is a complement C5 inhibitor used for atypical hemolytic uremic syndrome (aHUS). Phase III trials in adults and children suggest the standard dosing regimen provides troughs about 3-fold higher than needed to suppress the complement cascade. Ravulizumab trough monitoring as a tool for individualized dosing regimens has not been described in aHUS or in children. We describe maintenance ravulizumab use in a cohort of pediatric patients with aHUS, exploring potential for targeted dosing strategies using trough and AH50. Methods: This single-center, retrospective cohort study included pediatric patients with aHUS at remission receiving outpatient ravulizumab infusions between 6/30/23 and 3/31/24 with at least one ravulizumab trough. Patients received maintenance ravulizumab infusions according to the standard (SR) or a modified (MR) regimen at the discretion of the nephrologist. The primary objective was to describe troughs and corresponding AH50 for patients on at least two equal doses. Secondary, exploratory outcomes included comparison of troughs for patients receiving SR and MR, and for patients with multiple troughs. Frequency of potential adverse drug events (pADE) and estimated drug costs are reported. Results: Nine patients with 28 drug levels were included. The median weight was 17.2 kg (IQR 12.0-39.3) at ravulizumab initiation and 19.1 kg (IQR 14.6-50.8) at first trough. Four patients (44%) received a MR, where dose was not increased for weight gain (n=4) and frequency was extended due to scheduling conflicts (n=1). Rationale for MR included elevated troughs (n=4), clinical stability (n=4), and concern for pADE (n=1). The mean ravulizumab trough for the cohort was 399.9 mcg/mL (SD 104.6). All troughs exceeded goal of 175 mcg/mL and achieved AH50 <10%. There was no difference in troughs between patients receiving SR and MR (diff 30 mcg/mL, 95%CI -131 to 192). For patients with multiple troughs, intra-patient variability was low (CV <25%). Rates of pADE were similar between regimens and drug cost of MRs were lower. Conclusion: Individualized ravulizumab regimens based on trough and complement monitoring seems to be safe and effective while reducing drug costs. Further study is needed to better understand impact on lab and clinical parameters to determine optimal ravulizumab regimen.