Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome: an update

Background: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by platelet consumption, hemolysis, and organ damage. Eculizumab (ECU), a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule is not yet clear. Methods: Here, we report our experience with ECU maintenance treatment and the interval between subsequent doses being extended based on global classical complement pathway (CCP) activity aimed at <30% for maintaining aHUS into remission. Results: We report on 38 patients with aHUS, 13 children, 21 female, with a median age of 25.0 years (range 0.5–60) at disease onset treated with ECU standard schedule for a median of 2.6 months (range 0.4–24.6). Once stable TMA remission was obtained, the interval between ECU doses was extended based on complement function, with a target CCP activity of <30%. With this approach, 22 patients regularly receive ECU infusion every 28 days and 16 every 21. During a median observation period on ECU, an extended interval of 26.9 months (range 0.8–80.9), with a cumulative observation period of 1,208 months, none of the patients relapsed. Conclusion: Monitoring complement activity allows a safe reduction in the frequency of ECU administration in aHUS while keeping the disease in remission.