Jenny Powers

June 07, 2012

June 7, 2012 (Paris, France) — Children with atypical hemolytic-uremic syndrome (aHUS) had a robust response to eculizumab (Soliris) in real-life clinical settings. The finding mirrors clinical trial results reported for adults and teens.

Therese Jungraithmayr, MD, from the Innsbruck Medical University in Austria, presented results of a study conducted at several North American centers and centers from 6 European countries here at the XLIX European Renal Association-European Dialysis and Transplant Association Congress. The researchers recommend that eculizumab be the standard of care for patients with aHUS.


Although aHUS affects only an estimated 7 in 1 million children, it is life threatening. It mainly affects children and young adults, Dr. Jungraithmayr explained. aHUS is characterized by rapid progression to systemic thrombotic microangiopathy (TMA), resulting in renal and multiple organ failure. Within the first year of diagnosis, 65% of patients require dialysis or die. Plasma exchange/infusion (PE/PI) is used to treat the condition, but 33% to 40% of patients receiving PE/PI progress to end-stage renal disease or die during the first manifestations of aHUS.

aHUS results from chronic uncontrolled complement activation that, in turn, activates platelets and endothelial cells. Eculizumab is an antibody to the C5 protein that breaks this cycle by binding to C5 and preventing formation of the activation complex.

In clinical trials, eculizumab prevented progression to end-stage renal disease, with patients even regaining renal function and showing a reversal of organ damage.

Study Results

This retrospective study evaluated the efficacy and safety of eculizumab in 19 children with aHUS from a cohort of 30 adults and children who were treated outside the clinical study environment. Fifteen patients were 2 to 11 years of age; the remaining 4 were 12 to 17 years of age. All patients received 1 or more doses of eculizumab outside clinical trials, sponsored by Alexion Pharmaceuticals, conducted from 2007 to 2009.

At baseline, 8 (42%) patients had a platelet count below 150 × 109/L. The estimated glomerular filtration rates (eGFR) was below 30 mL/min per 1.73 m² in 6 (32%) patients. Complement regulatory factor (CRF) mutations or anti-CRF antibodies were identified in 10 (53%) patients.

Patients received eculizumab therapy for a median 6 months (range, 1 to 16 months).

In the cohort, 17 (89%) patients achieved normalized platelet counts with eculizumab, including 7 of 8 (88%) patients who had abnormal counts at baseline. The effect on platelet count in responding patients occurred 1 week after eculizumab administration and was maintained during treatment.

Improved renal function (an increase in eGFR of at least 15 mL/min per 1.73 m²) was seen in 9 (47%) patients. These same patients showed a 1-stage improvement in chronic kidney disease and a decrease in serum creatinine of at least 25%.

In a subgroup of 11 patients who had a current TMA manifestation lasting less than 2 months, 8 (73%) achieved improved renal function.

Dr. Jungraithmayr explained that "this demonstrates that early intervention with eculizumab is associated with greater renal function improvement. It is also important to note that eculizumab ended dialysis for 50% of the patients already on dialysis, and no patients needed to begin dialysis."

TMA event-free status, defined as stable platelets requiring no PE/PI or dialysis, was achieved by 13 (68%) patients. Median TMA intervention rate, or the number of times PE/PI or dialysis was required by a patient per day, was significantly reduced, from 0.31 to 0.08 (range, 0.00 to 2.38; = .0001). The TMA intervention rate decreased from a median of approximately 2 PE/PI per week to a median of 0 interventions in all 19 patients, and was maintained for the entire study period. Of the 6 patients who did not achieve TMA event-free status, 5 discontinued treatment early and 1 had fewer than 12 weeks of follow-up.

Summary of Findings

Eculizumab had the same efficacy in patients with and without known mutations, irrespective of patient age. Improved platelet counts were achieved by 93% of patients younger than 12 years and by 89% of those 12 years and older; TMA event-free status was achieved by 73% and 68%, respectively, and improved eGFR was seen in 53% and 47%, respectively.

Overall, 15% of patients reported adverse events — mainly pyrexia, diarrhea, vomiting, and cough. One patient with a history of carotid artery stenosis died after carotid artery recanalization complications; that death was not considered to be drug related.

Eculizumab: Standard of Care for aHUS Patients of Any Age?

Lucio Manenti, MD, from the division of nephrology at the Arcispedale Santa Maria Nuova in Reggio Emilia, Italy, told Medscape Medical News that "eculizumab could indeed be an option for renal diseases other than aHUS, in particular membranoproliferative nephropathy forms secondary to complement regulation abnormalities, and all the forms of primary glomerulopathies evolving into aHUS or with superimposed signs of thrombotic microangiopathy and systemic hemolysis, such as systemic lupus erythematosus and possibly vasculitis and IgA nephropathy."

The researchers conclude that these findings from children with aHUS are consistent with efficacy and safety outcomes from prospective clinical trials of adolescents and adults with aHUS, and support the role of eculizumab as a new standard of care for aHUS patients of any age.

Dr. Manenti echoed this recommendation. "Regarding the use of eculizumab in primary aHUS (without clear underlying/associated clinical conditions such as malignancies, infections, drugs), eculizumab could be considered the standard of care."

The study was supported by Alexion. Dr. Manenti has disclosed no relevant financial relationships. Dr. Jungraithmayr reports serving on the advisory board of Alexion.

XLIX European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress: Abstract FO064. Presented May 25, 2012.