ESPN 50th Annual Meeting

ESPN 2017

Improved outcomes for paediatric patients with atypical haemolytic uraemic syndrome (aHUS) receiving long-term eculizumab treatment during on-treatment periods compared with off-treatment periods
Lars Pape 1 Chris Mix 2 Jimmy Wang 2 Larry Greenbaum 3 Anne-Laure Lapeyraque 4

1- Hannover Medical School, Hannover, Germany
2- Alexion Pharmaceuticals, New Haven, CT, USA
3- Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA, USA
4- Chu Sainte-Justine, Montréal, Québec, Canada

To assess thrombotic microangiopathy (TMA) risk and long-term outcomes in paediatric aHUS patients on eculizumab treatment compared with off-treatment periods. 

Material and methods:

This is a long-term, observational, follow-up study of paediatric patients with aHUS treated with eculizumab in previous clinical studies (NCT01522170; March 2016 data-cut). TMA rate, change in renal function and targeted serious adverse events (TSAE: serious infections, meningococcal infection, sepsis, leukopenia, infusion reactions, renal or hepatic impairment and malignancy) were assessed.


Thirty-nine patients with a median age of 8.0 years (range 0.0–17.0) at first eculizumab infusion were enrolled in the study. No on-treatment data was collected from four patients who stopped treatment prior to this study. In the primary studies, median time between aHUS diagnosis and first eculizumab dose was 3.1 (range 0.0–191.4) months. Median follow-up duration in this study was 40.6 (range 3.1–84.7) months.

Seventeen (44%) patients had at least one off-treatment period, of whom nine (53%) restarted treatment. During eculizumab on-treatment periods, the protocol-defined TMA manifestation rate was 8.6/100 patient-years vs 29.3/100 patient-years for off-treatment periods (Table). In a post-hoc analysis, when TMA manifestation excluded patients who only had a change in one laboratory criterion, the rates were 2.3 and 22.8 per 100 patient years during on- and off-treatment periods, respectively. When on-treatment, two patients (1.6/100 patient years) developed meningococcal infections vs none off-treatment. Two deaths occurred, one on-treatment (possibly related to treatment) and one off-treatment. No other TSAEs were identified. 


This is the largest study of paediatric patients with aHUS treated with eculizumab to date. Eculizumab was generally well-tolerated in paediatric patients throughout the study. Patients in the on-treatment periods had a reduced rate of TMA manifestations compared with off-treatment periods.