Atypical haemolytic uraemic syndrome (aHUS) is a life-threatening disease caused by uncontrolled complement activation with poor outcomes. We describe results from the first prospective paediatric clinical trial of patients with aHUS treated with eculizumab, a terminal complement inhibitor.
An open-label, single-arm trial of eculizumab in paediatric pts with aHUS. The primary endpoint was complete TMA response (normalization of platelets and LDH, and ≥25% improvement in serum Cr from baseline) at 26 wks. Dosing was based on weight cohorts. Inclusion criteria included platelet count <150x109/L, serum creatinine ≥97th percentile for age at screening and LDH ≥1.5´ upper limit of normal. An identified complement mutation was not required. Patients with Shiga toxin-producing E. coli (STEC)-HUS or severe ADAMTS13 deficiency (activity <5%) were excluded.
In total 22 patients were enrolled and 19 (86%) completed 26 weeks of treatment. Baseline characteristics and outcomes are shown in Table. At 26 weeks all patients had discontinued plasma exchange; 9/11 on dialysis at baseline had discontinued dialysis. Eculizumab was well tolerated. No meningococcal infections or deaths occurred and no safety concerns arose.
Eculizumab treatment inhibited complement-mediated TMA as well as improved haematologic and renal outcomes. Early intervention with eculizumab is effective and well tolerated in paediatric patients with aHUS.
