Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening disease of chronic, uncontrolled complement activation, leading to platelet activation, thrombosis, hemolysis, and thrombotic microangiopathy (TMA). Despite PE/PI, up to 65% of patients (pts) sustain permanent renal damage, progress to end-stage renal disease, or die within 1 year (yr) of diagnosis. Significant hematologic and renal improvements were demonstrated in pts with progressing TMA who were treated with eculizumab (Ecu) in a Phase 2 trial. The current analysis was undertaken to gain further insight into the timing of those hematologic and renal improvements.


Pts ≥12 yrs of age with progressing TMA (platelet count<150×109/L despite ≥4 PE/PI sessions in the week [wk] prior to screening) enrolled in a 26-wk single-arm, Phase 2 trial of Ecu with a long-term extension period. Change from baseline in platelet count, LDH, hemoglobin (Hb), haptoglobin (Hp), creatinine (Cr) and eGFR were measured. The timing of platelet normalization (≥150x109/L), hematologic normalization (platelet normalization and LDH ≤ULN), Cr decrease (≥25%) and eGFR increase (≥15 mL/min/1.73 m2) – all for ≥2 consecutive measurements ≥4 wks apart – were assessed over the study period.


Seventeen pts (median, 28 yrs; 71% female; 41% with prior renal transplant) enrolled and 15 continued into the long-term extension. The median time from diagnosis to screening was 10 months, and the median time from the onset of the current clinical manifestation was 0.75 months. The median duration of Ecu exposure at the data cut was 100 wks. Mean baseline values were as follows: platelet – 109.0x109/L; LDH – 323 U/L; Hb – 89 g/L; Hp – 0.5 g/L; Cr – 352 μmol/L; eGFR – 22.9 mL/min/1.73 m2.

Significant improvements in mean platelet count from baseline were seen within the first wk of Ecu treatment and were sustained throughout the study period (Figure 1a). Significant and rapid improvements from baseline in Hb and Hp are shown in Figures 1b and 1c. With ongoing Ecu treatment, platelet and hematologic normalization was reached starting at wk 4 (the first assessable time point based on the criteria definition), with the majority of pts achieving normalization by wks 6 and 26, respectively (Figure 2A). With ongoing Ecu treatment, the threshold for both Cr decrease and eGFR increase were met as early as wk 6 in some pts, with the majority meeting these thresholds by wks 10 and 38, respectively. (Figure 2B). Earlier Ecu intervention (shorter duration of aHUS clinical manifestation prior to treatment) was associated with greater increases in eGFR (P<0.01).


Initial platelet count and LDH normalization was observed at the first assessable time point, with the majority of pts achieving normalized levels by 6 months. Renal function also improved rapidly, with the majority of pts reaching the threshold for Cr and eGFR improvement by 9 months. These results illustrate that, in this population of pts with progressing TMA, early and ongoing treatment with Ecu led to rapid improvements in hematologic and renal parameters, demonstrating sustained TMA control.

Figure 1. Platelet count change (a), mean hemoglobin (b), and haptoglobin (c) from baseline through 2 years

Figure 2. Cumulative % of pts reaching key hematologic (a) and renal (b) endpoints over time


Bedrosian:ALexion Pharmaceuticals: Employment. Furman:Genentech: Consultancy, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Gilead: Consultancy.

Author notes


Asterisk with author names denotes non-ASH members.