SaO008NORMALISATION OF RENAL FUNCTION FOLLOWING EARLY INITIATION OF ECULIZUMAB IN PATIENTS WITH ATYPICAL HAEMOLYTIC URAEMIC SYNDROME: POOLED ANALYSIS OF PROSPECTIVE CLINICAL TRIALS

Abstract

Introduction and Aims: Atypical haemolytic uraemic syndrome (aHUS) is a serious, life‐threatening condition. It is caused by genetic abnormalities in the complement system, leading to chronic, uncontrolled complement activation. This results in systemic thrombotic microangiopathy (TMA), which can quickly progress to severe renal and other end‐organ damage. Therefore, rapid initiation of appropriate therapy is important. Here we report analysis of pooled data from four clinical trials of the terminal complement inhibitor, eculizumab (Ecu), to evaluate the outcomes of early (≤7 days of aHUS manifestation) versus later Ecu initiation (>7 days) in terms of renal function. Methods: Data were pooled from four prospective phase 2, open‐label, single‐arm trials, which included both paediatric and adult patients with aHUS. Inclusion required a documented date of onset of current TMA manifestation and a baseline eGFR of <90 mL/min/1.73m2. The percentage of patients with normalised eGFR (≥90 mL/min/ 1.73m2) and the time to platelet count normalisation (≥150 x 109/L) were evaluated. Results: Data from 97 patients were analysed: median (range) age at enrolment was 29 (0‐80) years; 62% of patients were females; median (range) duration of current manifestation to start of Ecu treatment was 23 (1‐1447) days; median (range) baseline eGFR was 15.9 (5.6‐76.1) mL/min/1.73m2. Ecu treatment was started in 21 patients in ≤7 days and 76 patients in >7 days after current presentation with TMA. Median eGFR was 11 mL/min/1.73m2 for patients started in ≤7 days and 16 for those initiating >7 days. The percentage of patients with normalised eGFR was consistently higher at all timepoints for the early administration group (see figure). The mean (SE) change in eGFR at 2 years was 50.7 (28.5) mL/min/1.73m2 in the early administration group and 26.9 (5.6) mL/min/1.73m2 in the later group. The mean (SD) time to platelet count normalisation was 14.3 (20.3) and 27.8 (38.7) days in the early and later groups, respectively. Conclusions: Results of this pooled analysis indicate that patients with aHUS benefit from early administration of Ecu within 7 days of a TMA manifestation, with greater and more sustained improvements in platelet count and in eGFR. These data emphasise the importance of rapid diagnosis and treatment of aHUS for recovery of renal function. (Figure Presented).