Eculizumab Changed the Course of Atypical Hemolytic Uremic Syndrome

By Rob Goodier

June 12, 2019

NEW YORK (Reuters Health) - The approval of the monoclonal antibody eculizumab for treatment of atypical hemolytic uremic syndrome led to significant improvements in outcomes, according to a study of French patients presented June 3 at American Transplant Congress 2019 in Boston.

From five years before the drug was introduced to five years afterward, rates of chronic dialysis among patients with the rare kidney disease fell from 34% to 16%, and kidney transplantation increased from 46% to 72%. At the same time, eculizumab treatment increased from 20% to 44% in all aHUS patients with transplanted kidneys, researchers reported.

"Nearly 60% of the deaths among aHUS patients during the study period occurred in patients undergoing chronic dialysis. A voluntarist policy of kidney transplantation in the aHUS population with tailored eculizumab prophylaxis should eventually save life years, and should therefore be strongly advocated," the study's lead author, Dr. Julien Zuber, Professor of Clinical Immunology and Nephrology at the teaching hospital Necker in Paris France, told Reuters Health by email.

Dr. Zuber and colleagues studied data from 34 French medical centers, following 397 patients from 2007 to 2016. Eculizumab, sold as Soliris by Alexion Pharmaceuticals, was approved in Europe for the treatment of aHUS in November 2011. It had been approved in the U.S. a month earlier.

In a large sub-group of aHUS patients with end-stage renal disease, the rate of transplantation increased from nearly 22% to 60% among those carrying a CFH gene mutation, the most common genetic risk factor for aHUS.

The percentage of patients with CFH mutations and other genetic variations that affect the body's complement system did not change over the study period, suggesting that the introduction of eculizumab accounts for the renal outcome improvements, according to the research.

"This nationwide study demonstrates that the outcome of kidney transplantation in aHUS patients has dramatically improved since the approval of eculizumab. This led to unprecedented and compelling changes in the epidemiology of aHUS disease," Dr. Zuber says.

The disease primarily affects the kidney, causing blood clots that can lead to hemolytic anemia, thrombocytopenia, and kidney failure. Fortunately, it is rare, afflicting an estimated 1 in 500,000 people per year in the United States, according to the US National Library of Medicine.

"In this large multicenter trial, the use of eculizamab in patients with atypical hemolytic syndrome has improved their access to transplantation, allowing more patients to get kidney transplants and get off dialysis. This is good news for patients with atypical HUS awaiting a kidney transplant," Dr. Devin Eckhoff told Reuters Health by email. Dr. Eckhoff, the Arnold G. Diethelm Chair in Transplantation Surgery at the University of Alabama, Birmingham, was not involved in the study.


American Transplant Congress 2019.