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

Abstract Background Ravulizumab drug monitoring has not been explored for maintenance therapy in patients with atypical hemolytic uremic syndrome (aHUS). Phase III trials suggest standard dosing regimen provides troughs about 3-fold higher than needed to suppress complement activity. We describe the use of ravulizumab in pediatric patients with aHUS in remission, exploring potential modified dosing strategies based on serum drug level and complement markers. Methods This single-center, retrospective cohort study included pediatric patients with aHUS in remission receiving outpatient ravulizumab infusions between June 30, 2023 and March 31, 2024 with at least one ravulizumab trough. Patients received a standard (SR) or a modified (MR) regimen, determined by the nephrologist. The primary outcome was to describe troughs and corresponding AH50 for patients on at least two equal doses. Secondary outcomes included comparison of troughs by regimen, intra-patient variability, possible adverse drug events (pADE), and drug costs. Results Nine patients were included. The mean ravulizumab trough level was 399.1 (± 107.3) mcg/mL. All patients exceeded goal of 175 mcg/mL and achieved AH50 < 10%. Four patients (44%) received ravulizumab according to a MR. No difference was observed in ravulizumab trough levels between SR and MR groups (p = 0.67). Patients with multiple troughs showed low intra-patient variability (CV < 25%). pADE rates were similar across regimens, and MR was associated with lower drug costs. Conclusion Individualized maintenance regimens of ravulizumab based on trough and complement monitoring appears safe and effective while reducing drug costs. Further study is needed to define optimal ravulizumab maintenance dosing strategy.