Rapid, sustained aHUS response seen with Ultomiris in real-world data
Many patients normalized key blood and kidney markers during the first year
Written by |
Treatment with Ultomiris (ravulizumab) led to both rapid and long-lasting improvements in people with atypical hemolytic uremic syndrome (aHUS), according to a real-world study.
The study found that most people who had never received a C5-inhibitor therapy before saw key blood and kidney measures return to normal. These improvements began as early as four to eight days after starting treatment and were maintained for up to one year.
“This study reported data from early time points after [Ultomiris] initiation (Day 4) that suggest immediate improvement in clinical parameters,” the researchers wrote. It also contributed to “build a robust evidence base for making informed decisions about the use of [Ultomiris] in this patient population.”
The study, “Real-World Effectiveness of Ravulizumab Among C5 Inhibitor-Naive Patients With Atypical Hemolytic Uremic Syndrome: A Physician Panel-Based Chart Review (a HUS IMPACT Study),” was published in Kidney Medicine and funded by Alexion, AstraZeneca Rare Disease, the company that markets Ultomiris.
What drives aHUS and how Ultomiris works to control it
aHUS is caused by the abnormal activity of the complement cascade, part of the immune system, which leads to tiny blood clots forming in small blood vessels. This process is called thrombotic microangiopathy (TMA). The most common symptoms are red blood cell destruction (hemolysis), low red blood cell levels (anemia), low platelet counts, and kidney failure.
Ultomiris is an antibody-based therapy that blocks part of the complement pathway. It works by stopping the C5 protein from splitting into the C5a and C5b fragments, which helps shut down the process that leads to blood clotting and organ damage.
To better understand how Ultomiris works in everyday clinical practice, researchers in the U.S. reviewed medical records from 79 adults with aHUS who had never previously received a C5-targeted treatment.
The median age was 44.3 years at diagnosis and 44.4 years when Ultomiris treatment began. About 59.5% of the participants were men. Among those with available data, 65.8% had no family history of aHUS, and 59.5% had a known trigger for the disease. Genetic changes affecting the complement cascade, most often in the CFH and CFHR1 genes, were found mainly in patients whose aHUS was triggered by an autoimmune disease.
About one-third of the patients received plasma exchange before starting Ultomiris, and three had previously undergone a kidney transplant. Plasma exchange replaces the liquid part of the blood (plasma) to help remove overactive immune proteins that drive aHUS.
Patients showed early and continued clinical improvements on Ultomiris
Over the first year of treatment, patients showed significant improvements in key blood and kidney measures, with some changes appearing as early as four to eight days after starting Ultomiris. Levels of lactate dehydrogenase (LDH), a marker of hemolysis, and blood creatinine, a marker of kidney damage, dropped significantly by day four. Platelet counts began to rise by day eight.
By one year, most patients saw these measures return to normal ranges: platelet counts (83.3%), blood serum creatinine (87.5%), LDH (92.1%), estimated glomerular filtration rate (78.6%) — a measure of kidney function — and hemoglobin (74.5%).
A complete TMA response, meaning normal platelet and LDH levels along with improved kidney function, was achieved by 60% of patients at six months and 68% at one year.
Among the 20 patients who had needed dialysis in the year before or shortly after starting Ultomiris, 70% were able to stop dialysis afterward. Dialysis filters waste and excess fluid from the blood when the kidneys are not working as they should.
Twenty patients stopped Ultomiris within the first year, after a median treatment duration of 8.6 months. The most common reasons were that doctors felt the treatment course was complete, kidney function had stabilized or normalized, or the treating physician chose to stop therapy.
“This study provides real-world evidence to support the immediate and sustained benefits of initiating [Ultomiris] in patients with aHUS, as seen by the early response and continued improvement in clinical outcomes,” the researchers wrote.
