aHUS drugs restore kidney function in 60% of patients in Romania
Eculizumab, ravulizumaba found safe, effective in real-world study
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Eculizumab and ravulizumab — treatments for atypical haemolytic uremic syndrome (aHUS), available in the U.S. as Soliris and biosimilars, and as Ultomiris, respectively — were found to safely lead to a complete recovery of kidney function in about 60% of people with the rare autoimmune disease in Romania.
That’s according to the results of a new study, conducted at a single center in Romania, that also found a relatively long delay in diagnosis and treatment start for aHUS patients in the European nation. Additionally, the researchers found that mutations in the CFI gene were identified more frequently than previously reported.
“We provided for the first time data on clinical presentation, genetic profiles, and outcomes in aHUS patients treated with [eculizumab and ravulizumab] in Romania,” the team wrote, noting that these therapies, both given intravenously, or into the vein, were found to be “effective and safe.”
“Our data suggest creation of a National aHUS Registry and of a standardized protocol of management, and increased physicians’ awareness to improve aHUS care,” the researchers wrote.
The study, “Terminal complement inhibition in atypical haemolytic uremic syndrome: a single-centre experience,” was published in the journal Frontiers in Pharmacology.
aHUS is caused by the abnormal activity of the body’s complement cascade, which leads to the formation of blood clots in small vessels. This is known as thrombotic microangiopathy, or TMA. The most common symptoms are red blood cell destruction, called hemolysis, and consequent low levels of these cells, known as anemia, as well as low platelet levels and kidney failure. Platelets are small cell fragments in the blood that help with clotting.
Most people with aHUS have mutations in genes that regulate the complement system, a part of the immune system. However, a triggering event, such as an infection, is typically needed to develop the disease.
First study to investigate disease treatment in aHUS in Romania
To learn more about the disease’s treatment in their country, a research team in Romania conducted a retrospective study involving 27 people with aHUS who started therapy with the complement inhibitors eculizumab and ravulizumab between January 2017 and January 2025. These patients had a median age of 30, and slightly more than half (59%) were female.
No patient had a family history of the disease, and in 44%, symptoms started during childhood. In two-thirds of the patients, the disease was triggered by infections. The median time from the most recent acute aHUS event to referral was 30 days. Approximately one-third of the patients experienced several aHUS events before admission.
At admission, most had acute kidney injury (89%), microangiopathic anemia (92%), and low platelet levels (80%), with 76% showing all three symptoms. Three-quarters of the patients had severe kidney injury, and 59% required dialysis.
The researchers noted that all patients had at least one issue besides kidney injury. These co-occurring conditions most commonly involved the central nervous system, comprising the brain and spinal cord (37%), the digestive tract (25%), or the cardiovascular system or (15% each).
Laboratory work showed signs of advanced chronic kidney disease, as indicated by a low estimated glomerular filtration rate (eGFR), and hemolysis. About three-quarters had low levels of C3 and high C5b-9, both indicating complement system activation.
Genetic testing was performed in 23 patients, 74% of whom had mutations in complement-related genes. These most frequently were the genes CFH/CFHR, CFI, C3, and CD46, but included seven new mutations representing potential risk. According to the researchers, these “findings suggest a relatively long delay in aHUS diagnosis and potential genetic difference in distribution of genes variants within the Romanian population, with CFI mutations more frequently observed.”
Approximately one quarter of the patients lacked disease-causing mutations but carried 2-4 aHUS risk factors. This group had significantly greater kidney impairment at admission and a more pronounced decline in eGFR at last follow-up, as assessed by eGFR, the data showed. Also, a lower proportion of patients remained dialysis-free.
“These findings suggest that patients with multiple risk factors — even in the absence of [disease-causing] mutations — may experience more severe [kidney] impairment than those with identified genetic variants,” the investigators wrote.
70% of patients on dialysis able to stop within 3 weeks of treatment
Treatment with eculizumab was started when aHUS was suspected, with patients switched to ravulizumab once a diagnosis was confirmed.
Following treatment, kidney function rapidly improved, with 26% of patients achieving partial kidney recovery after a median of 7.5 days, and 61% experiencing a complete kidney recovery after a median of 20 days, the data showed. Among individuals on dialysis, 70% were able to stop it within a median of 19.5 days.
Earlier therapy start was associated with better kidney outcomes, the researchers noted.
The therapy with [eculizumab and ravulizumab] was efficient and safe. However, improvement can be obtained by increasing physicians’ awareness for aHUS diagnosis.
Additionally, 85% of patients experienced a complete remission of microangiopathic anemia within a median of 78 days (about 2.5 months) when there was full remission, while platelet levels normalized in 93% of cases after a median of eight days. C3 levels normalized within 51 days, whereas those of C5b-c9 also normalized within 154 days, or about five months.
No severe adverse events or deaths were reported during treatment, and patients did not experience disease relapses.
“To our knowledge, this is the first report on aHUS patients diagnosed and treated with anti-C5 complement inhibitors in Romania,” the researchers wrote. “The therapy with anti-C5 monoclonal antibodies was efficient and safe. However, improvement can be obtained by increasing physicians’ awareness for aHUS diagnosis.”
