BACKGROUND:

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterised by hemolysis, platelet consumption and renal injury. Eculizumab, a monoclonal antibody blocking complement activity, has been successfully used in aHUS.

OBJECTIVES:

To optimise eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity.

PATIENTS/METHODS:

We studied 18 patients with aHUS (10 males, 8 females; age range 2-40 years) treated with eculizumab to induce and/or maintain disease remission. Patients were followed up for a cumulative observation period of 160 months during which blood samples were obtained at various time intervals to measure complement activity (Wieslab for the classical, alternative and mannose-binding lectin complement pathways) and the parameters of disease activity (haptoglobin, lactate dehydrogenase, platelet count). The intravenous eculizumab doses of 12-33 mg/kg were initially administered every week, with the interval between doses being gradually extended to two, three and four weeks on the basis of strict laboratory and clinical control.

RESULTS:

Complement activity was normal before eculizumab treatment, regardless of the state of the disease (activity or remission). It was completely suppressed one, two and three weeks after the last eculizumab infusion (mean values±SD: 1±1%-3±5% for both the classical and alternative pathways; p=0.0001 vs baseline), and partially suppressed after four weeks (22±26% and 16±27%; p=0.0001 vs baseline). The increase in the time interval between eculizumab infusions did not change disease activity markers.

CONCLUSIONS:

Monitoring complement tests can allow a safe reduction in the frequency of eculizumab administrations in aHUS while keeping the disease in remission.