Approved therapy works in preventing relapse in man with rare aHUS case
Newly ID'd disease-causing mutation thought to carry high risk of recurrence
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Treatment with Ultomiris (ravulizumab) successfully prevented disease recurrence in a middle-aged man whose atypical hemolytic uremic syndrome (aHUS) was linked to a novel mutation — one believed to put him at a high risk for relapse — in the CFH gene, a case report from Japan shows.
During the active phase of aHUS, after the patient was first evaluated, clinicians turned to plasma exchange, corticosteroids, and dialysis for treatment, “according to the Japanese guidelines,” the report noted. After remission, when genetic testing identified a high-risk mutation, Ultomiris was started with the goal of preventing recurrence during the chronic phase.
Over two years, the man had no signs of relapse, according to the researchers, with the case “resulting in a favorable outcome.”
Still, “because this is a single case, the efficacy and feasibility of long-term maintenance therapy with [Ultomiris] in the chronic phase cannot be established,” the team wrote.
The case was described in “Ravulizumab administration for relapse prevention in atypical hemolytic uremic syndrome with a CFH variant: A case report,” published in the journal Internal Medicine.
aHUS is caused by abnormal activation of the complement cascade, a part of the immune system, which leads to blood clotting in small blood vessels, known as thrombotic microangiopathy (TMA). Symptoms of aHUS typically include red blood cell destruction, called hemolysis, low levels of platelets, which are small cell fragments that help the blood to clot, and kidney damage.
Most people with aHUS have mutations in genes that help control the complement system, including the CFH gene, which makes a protein called complement factor H. However, these gene changes alone are usually not enough to cause the disease. A triggering event, such as an infection, is often needed for aHUS to develop.
Clinicians went on diagnostic odyssey to find cause of symptoms
Here, researchers described the case of a 40-year-old man with aHUS that ultimately was tied to a CFH gene mutation. Such mutations are commonly linked with severe disease and a high risk of recurrence.
The man sought hospital treatment after experiencing abdominal pain and nausea for five days.
At the first evaluation, the man had high blood pressure, a normal temperature, and mildly pale inner eyelids, a common sign of anemia. Laboratory findings revealed low red blood cell counts and elevated reticulocytes, or levels of immature red blood cells, as well as high lactate dehydrogenase (LDH) levels, indicating hemolytic anemia.
The patient also had low platelet counts and signs of kidney damage, such as elevated blood levels of creatinine and urea nitrogen, protein in the urine, and elevated urinary markers of kidney structural damage (beta2-microglobulin and N-acetyl glucosaminidase).
Based on these results, the patient was suspected of having TMA. He was started on plasma exchange therapy, dialysis, and high-dose corticosteroid therapy. Plasma exchange involves removing and replacing the liquid part of the blood to remove disease-causing components, while dialysis filters waste and excess fluid when the kidneys can no longer function normally.
After eight days of treatment, platelet levels increased, and LDH levels decreased, but the patient still had kidney dysfunction, according to the researchers.
Doctors ruled out diagnoses of thrombotic thrombocytopenic purpura (TTP), HUS caused by Shiga toxin-producing bacterial infection, severe infections, cancer, and drug-induced reactions.
A kidney biopsy revealed signs of inflammation in the kidneys’ filtering units (glomeruli) without any identifiable cause of infection, and damage without thrombotic lesions, consistent with a chronic phase of aHUS.
Treatment with Ultomiris started after genetic testing results
Further testing indicated complement dysregulation, and genetic testing confirmed the presence of a novel mutation (Glu1198Asp, c.3594A>T) in one copy of the CFH gene, which had not been previously described. Based on these results, the man was diagnosed with aHUS three months after initially seeking treatment.
Because patients with these mutations have a high risk of disease recurrence, preventive treatment with Ultomiris was started. Ultomiris is an anti-C5 antibody therapy, approved for adults and children with aHUS, that stops the complement cascade from overactivating and damaging blood vessels.,
Treatment with Ultomiris resolved the man’s hemolysis, according to the report. The researchers noted that his kidney function had gradually improved even before starting the therapy, allowing discontinuation of dialysis.
Over more than two years of treatment, the man had no clinical or laboratory evidence of disease recurrence. However, the researchers recommended that Ultomiris be continued due to the high risk of recurrence and progression to kidney failure from persistent or recurrent damage.
“Although it is not possible to determine whether earlier initiation of [Ultomiris] at the time of clinical diagnosis would have resulted in a more favorable clinical course, this case suggests that earlier consideration of anti-C5 antibody therapy after the diagnosis of TMA may have been warranted,“ the researchers wrote.
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