SO050LONG-TERM FOLLOW-UP STUDY OF ECULIZUMAB FOR PREVENTION OF THROMBOTIC MICROANGIOPATHY IN PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME

Introduction and Aims: In previous prospective clinical trials and a retrospective study, eculizumab prevented thrombotic microangiopathy (TMA) and improved renal function and hematologic parameters in 130 patients (pts) with atypical hemolytic uremic syndrome (aHUS). Pts could enroll in a long-term follow-up study to evaluate TMA event rates during eculizumab treatment and discontinuation. Methods: This is an ongoing, observational, multicenter study (NCT01522170) of aHUS pts treated with eculizumab in 5 prior clinical studies. Primary endpoint is TMA event rate post-parent study during on- (ON; among pts receiving eculizumab) and off-treatment (OFF; among pts who discontinued) periods. A secondary endpoint is TMA event rate ON per label (dose and interval) vs OFF. Results: The current study included 87 pts: 76 with ON and 39 with OFF periods with median follow-up of 26.1 and 20.1 months. Baseline clinical characteristics differed between groups (Table). OFF pts had higher estimated glomerular filtration rates at time of discontinuation than ON pts; 17 (44%) reinitiated eculizumab. TMA event rate was 63% lower ON vs OFF, and 74% lower for labeled dosing vs OFF (Table). OFF TMA events were more frequently severe (Table). Overall, TMA event rates were higher among pts with genetic mutations (9.8/100 patient-years for ON vs 34.5 for OFF) vs no mutation (2.8 vs 7.8) (hazard ratio, 4.5; P=0.0082).