Early initiation of eculizumab treatment in patients with atypical haemolytic uraemic syndrome improves long-term outcomes: a pooled analysis of clinical trials

Abstract

Introduction Atypical haemolytic uraemic syndrome (aHUS) is a severe, life-threatening disease requiring rapid treatment to inhibit complement-mediated thrombotic microangiopathy (TMA) and avoid irreversible organ damage. Four prospective clinical trials have reported the safety and efficacy of eculizumab (Ecu) in the treatment of aHUS [1,2]. We report data from a pooled analysis of these trials on renal function in patients starting Ecu within 7 days after the current aHUS manifestation. Methods Data from four phase 2, open-label, single-arm trials including both paediatric and adult patients with aHUS were pooled. Patients with a documented date of onset of current TMA manifestation and a baseline estimated glomerular filtration rate (eGFR) of <90 ml/minute/1.73 m2 were included. Changes from baseline in eGFR were analysed at study visits using a one-sample t test. Results Data from 97 patients were analysed: median (range) age at enrolment was 29 (0 to 80) years; 62% of patients were females; median (range) duration of current manifestation to start of Ecu treatment was 23 (1 to 1,447) days; median (range) baseline eGFR was 15.9 (5.6 to 76.1) ml/minute/1.73 m2. Ecu treatment was started in 21 patients in 7 days after presentation with TMA. Median eGFR was 11 ml/minute/1.73 m2 for the patients started within 7 days and 16 ml/minute/1.73 m2 for those initiating >7 days. The mean change from baseline in eGFR for patients starting Ecu in 7 days after presentation with TMA were 57 and 23 ml/minute/1.73 m2 at 1 year, respectively (Figure 1). Conclusion This pooled analysis indicates that patients treated with Ecu within 7 days of a TMA manifestation had a greater improvement in eGFR over time than patients in whom treatment was delayed. These data show the importance of rapid diagnosis and treatment of aHUS for recovery of renal function.