Soliris Effectively Treats aHUS in Newborn Girl, Case Study Reports

Soliris (eculizumab) may help to control microangiopathy — a disease affecting small vessels — and restore kidney function in newborns with atypical hemolytic uremic syndrome (aHUS), according to a recent case report.

The report, “Neonatal atypical hemolytic uremic syndrome in the eculizumab era,” was published in the journal AJP Reports.

aHUS is a rare disease in which the dysregulation of the complement cascade, a part of the immune system, causes blood clots to form inside small blood vessels. These clots prevent blood from flowing properly to various tissues and organs, especially the kidneys.

People with aHUS have low numbers of circulating red blood cells, as these tend to be destroyed faster than they are made (hemolytic anemia), as well as low numbers of platelets (thrombocytopenia), since these are constantly being used to form blood clots. The kidneys of these patients also tend to gradually lose their ability to filter waste products from the blood, and they eventually have kidney failure.

Soliris, an antibody-based therapy developed and marketed by Alexion, is one of the two medications currently approved to treat aHUS. It works by binding to C5, a specific component of the complement cascade. This makes the signaling cascade come to a stop, which in turn prevents excessive blood clotting.

Soliris is considered safe and effective in children, but its use is not approved in newborns and infants weighing less than 5 kg (about 11 lbs).

While aHUS rarely is seen in newborns, “its prognosis is poor, with a significant risk of progression to chronic kidney disease, recurrences, and fatal cases,” the researchers wrote.

A team in Portugal reported the case of a 5-day-old baby girl newly diagnosed with aHUS, for whom treatment with Soliris would prove effective at improving key blood components and kidney function.

The baby, a twin, was born at 36 weeks by emergency cesarean section, due to cord prolapse (when the umbilical cord slips out of the uterus) and pelvic presentation (when the fetus is positioned with the buttocks down).

In the first hour of life, she was pale and grunting, and responded poorly to stimuli. Blood analyses revealed she had too much acid in her blood (metabolic acidosis), high levels of lactate, and low blood pressure (hypotension). Administration of a salt solution improved metabolic acidosis, but not hypotension.

Additional blood analyses revealed she had hemolytic anemia, as indicated by low levels of hemoglobin — the protein responsible for transporting oxygen in red blood cells.

She also had thrombocytopenia, and showed signs of liver inflammation and/or damage, as indicated by high levels of liver enzymes, and had acute kidney injury, as indicated by high levels of urea and creatinine, two waste products.

These findings persisted over the following three days, despite treatment with red blood cell transfusions and a platelet concentrate.

Based on clinical and laboratory testing results, a diagnosis of aHUS was made.

Further testing revealed the baby had normal ADAMTS13 activity, an enzyme that can help distinguish aHUS from thrombotic thrombocytopenic purpura — another disease that can lead to the formation of blood clots in small blood vessels. However, genetic testing failed to identify any aHUS-predisposing mutations in complement genes.

When she was 5 days old, an infusion of fresh frozen plasma (the non-cellular portion of blood) began. Ten days later, she received her first dose of Soliris at 300 mg, the lowest recommended dose. Subsequent doses were given one week later, and every three weeks thereafter.

On Soliris, her levels of lactate dehydrogenase, a marker of tissue damage, normalized, and her creatinine levels dropped by 25% or more within seven days, reaching a normal range after 13 weeks. Her hemoglobin count rose to normal levels within 70 days (a little over two months).

She required red blood cell transfusions on days 18 and 40. In addition to Soliris, she was placed on antibiotics to prevent bacterial infections while at the hospital, as well as after discharge.

Meningococcal vaccines were given to her and to her closer relatives to protect against several types of meningococcal bacteria.

As of this report’s compilation, the girl was 20 months old and still on Soliris. Her blood counts and kidney function were normal. She was on the 15th to 50th percentiles for both weight and height, and had normal psychomotor development.

In this case, Soliris was effective in controlling the child’s microangiopathy and restoring kidney function.

“Nevertheless, there are still some debatable issues especially in neonates on when to start therapy, what dose to use, and how to monitor treatment and the timing of withdrawal,” the researchers wrote.

“aHUS is a disease that needs further prospective research to provide updated guidelines for an even more accurate management,” they concluded.