Shiga-toxin related HUS (STEC-HUS) in pediatric patients is severe with at least 50% of affected children requiring dialysis. Mortality rates can reach 5% and long-term renal sequels occur in 30% of surviving patients. No specific treatment has proven its efficacy. Activation of the complement alternative pathway (CAP), a well known pattern of atypical HUS (aHUS) has been postulated in STEC-HUS patients. Eculizumab (EC), a monoclonal C5 antibody, which inhibits CAP activation has been proposed in STEC-HUS patients with conflicting results. Considering the lack of therapy in STEC-HUS, controlled study of EC efficiency was mandatory.

Material and methods:

We conducted a multicentric, single blinded, versus placebo trial of EC in pediatric STEC-HUS patients. Patients under 18 years were randomized in a 1:1 ratio to receive either EC or placebo during 4 weeks. Follow-up lasted for 1 year after treatment. Primary end point was the occurrence of a dialysis >48h. Secondary end points included renal, hematological and other organs involvement. Safety was assessed throughout the course of the trial.

Results:

Of 100 patients who underwent randomization, 14 did not complete the trial. Among the 86 analyzed patients (42 in the placebo and 44 in the EC group) demographic characteristics were similar.  There was no difference in the occurrence of a dialysis >48h between the 2 groups (43% in the placebo and 57% in the EC group).  No difference was found in the general course of acute renal failure or in the occurrence of mid-term renal sequels (6 and 12 months after the treatment phase). Hematological involvements as well as extrarenal manifestations of the HUS were also similar between the 2 groups.

Conclusions:

In pediatric STEC-HUS patients, treatment with EC is not associated with either an improvement of the course of neither the acute phase of the disease nor a prevention of midterm renal sequels.