Eculizumab proves effective in treating atypical hemolytic uremic syndrome

Eculizumab proves effective in treating atypical hemolytic uremic syndrome

A new treatment for patients with atypical hemolytic uremic syndrome ( aHUS) was tested by researchers at Emory University. According to an article published in the New England Journal of Medicine, it seems that eculizumab, a monoclonal antibody, is effective in the management of this life-threatening inflammatory disease.
Hemolytic uremic syndrome, which is a thrombotic microangiopathy that causes blood clots in small vessels, is characterized by thrombocytopenia, hemolytic anemia and uremia. It mostly affects children up to 7 years old and is the most common cause of acute renal failure in children. The hemolytic uremic syndrome is often associated with enteric infections (E. coli, Shigella, Salmonella, etc.), but it can occur in other situations such as after certain drugs, tumors, after transplantation, etc..

Eculizumab

A few days after enteric infection multiple organ impairment can occur such as hepatosplenomegaly, petechiae, hypertension. These symptoms can sometimes be complicated with acute renal failure, convulsions, cardiac arrhythmias, hepatitis and even death. So far atypical hemolytic uremic syndrome (aHUS) has been treated with plasma exchange or infusion, but not all patients respond to this treatment. The rate of kidney failure or even death occurs in 30-40% of cases during the first clinical episode. In addition, in the first year, up to 65% of patients treated with plasma exchange or infusion develop renal or die.

Eculizumab, the new treatment tested for hemolytic uremic syndrome, blocks the production of inflammatory proteins by binding to complement C5 protein. FDA has approved eculizumab as previous studies have shown that this monoclonal antibody is useful for the treatment of paroxysmal nocturnal hemoglobinuria and now studies show its effectiveness in the treatment of aHUS.

There were conducted two phase 2 clinical trials that included 37 patients who did not responded to plasma exchange or infusion or had no platelet count decrease >25% for 8 weeks during standard treatment. After being treated for 26 weeks, it was found that patients who received eculizumab had an increase in platelet count and TMA (thrombotic microangiopathy) event-free status. The study results also showed that eculizumab significantly improved patient status: hematological measurements were normalized and platelet increased from baseline.

Other improvements were made on kidney function: 4 of 5 patients receiving dialysis were able to discontinue dialysis after treatment with eculizumab. It should be noted that there were no cases of severe toxicity or adverse reactions to treatment. Principal investigator Larry Greenbaum, MD, PhD, said: “This study showed that eculizumab is effective in treating patients with this chronic, life-threatening disease, and we were pleased to be one of the participating sites.”