Eculizumab for Atypical Hemolytic-Uremic Syndrome

For patients with atypical hemolytic-uremic syndrome, treatment with the terminal complement inhibitor eculizumab can improve renal function, even allowing some patients to discontinue dialysis, reports a study in the New England Journal of Medicine.

The report describes two prospective phase 2 trials of eculizumab in patients with atypical hemolytic-uremic syndrome, aged 12 years or older. Trial 1 included 17 patients with low platelet counts and kidney damage. Trial 2 included 20 patients with kidney damage but no more than a 25 percent reduction in platelet count during at least 8 weeks of plasma exchange or infusion. Both trials included 26 weeks of eculizumab; with long-term extension phases, treatment continued for a median of 64 and 62 weeks, respectively.

In trial 1, platelet count increased by a mean of 73 × 109 over 26 weeks. In trial 2, 80 percent of patients remained free of thrombotic microangiopathy events—including dialysis initiation—while receiving eculizumab.

Eculizumab was also associated with time-dependent improvement in estimated GFR, particularly in patients receiving earlier treatment. In trial 1, four out of five patients were able to discontinue dialysis. Long-term treatment with eculizumab had no cumulative toxicity or serious infection-related adverse events, including meningococcal infections.

Atypical hemolytic-uremic syndrome—caused by genetic defects in complement system regulation—puts patients at risk of complement-mediated thrombotic microangiopathy affecting the kidneys and other organs. The new trials support previous case reports showing benefits of complement inhibitor therapy with eculizumab.

These benefits include improved renal function even in patients with significant, long-standing renal damage. The researchers conclude, “The results of eculizumab therapy appear to represent a substantial advancement in the treatment of patients who have this severe and life-threatening systemic disease” [Legendre CM, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013; 368:2169–2181].

July 2013 (Vol. 5, Number 7)