Soliris effective for Latin America patients, but accessibility remains a problem
Researchers reviewed 25 studies that reported data from 376 adults, children
The use of Soliris (eculizumab) is changing the natural course of atypical hemolytic uremic syndrome (aHUS) in Latin America as it has in other regions, helping many patients achieve better outcomes, according to a review study.
While aHUS arises from the same genetic causes and manifests in a similar way to other regions, adults and children in Latin America may have limited access to diagnosis and treatment.
“Addressing economic challenges and investing in healthcare infrastructure will be essential to implement strategies for timely detection and early treatment of aHUS in Latin America,” wrote researchers in Argentina, Brazil, Chile, Colombia, and Mexico. The study, “Clinical presentation and management of atypical hemolytic uremic syndrome in Latin America: a narrative review of the literature,” was published in Expert Review of Hematology.
aHUS occurs when blood clots form in small blood vessels, blocking the normal flow of blood to organs and causing red blood cells to break down. While genetic mutations increase the risk for aHUS, they’re often not enough to cause it. Symptoms of aHUS usually manifest after a trigger like an infection.
Aside from being a rare disease, information about aHUS is relatively limited outside Europe and North America, leading the researchers to skim the scientific literature for studies about how the disease manifests and is treated in Latin America.
‘Consistent’ with other parts of the world
They identified 25 relevant studies published from 2013 to 2022 that reported data from 376 adults and children with aHUS from one of four countries — eight (32%) from Argentina, eight (32%) from Colombia, seven (28%) from Brazil, and two (8%) from Chile.
Most studies (72%) focused on the clinical presentation and outcomes of aHUS, with 11 being case reports. Four (16%) focused on the results of genetic testing in Argentina. The other three (12%) described issues of access to Soliris, including shortages and costs.
Common triggers for aHUS in adults included pregnancy or the period after giving birth, infection, and medications that cause thrombotic microangiopathy, or low numbers of platelets and red blood cells along with organ damage due to blood clots. In children, the most common trigger was an infection.
Patients often presented with digestive problems, high blood pressure, and altered neurological function, along with low circulating levels of C3, a protein of the complement system, which is part of immune system, and hemoglobin, which carries oxygen in red blood cells. A waste product called creatinine was often higher than normal, a sign of damage to the kidneys.
The proportion of patients who carried mutations in genes linked to aHUS ranged from 42% in a study from Argentina to 89% in Brazil. Up to about half the mutations were identified as pathogenic, that is, disease-causing, or likely to cause disease.
Most mutations mapped to the CFH gene, which codes for a complement protein. Other genes also had mutations, but their frequency varied widely, perhaps due to differences in genetic testing. For example, a CFHR1-R3 deletion was found in up to a third (33%) of the patients in Brazil, but wasn’t reported in other countries.
“Available data about aHUS in Latin American countries indicate that disease characteristics and management approaches are consistent with those reported in the rest of the world,” the researchers wrote.
aHUS treated with Soliris
Three studies showed the benefits of Soliris over plasma exchange, a blood “cleaning” procedure. For example, in a Brazilian study of 34 patients where 65% received plasma exchange and 91% Soliris, more patients stopped dialysis after starting Soliris. Children started Soliris sooner than adults (30 vs. 260 days).
A monoclonal antibody, Soliris works by binding to the complement protein C5 to keep it from cleaving into two separate molecules that ultimately lead to blood clotting.
In Colombia, eight of 20 patients were treated with Soliris and plasma exchange and had better outcomes than those on plasma exchange alone. Early treatment improved organ function within four weeks.
Two studies in Argentina reported the use of dialysis, transfusions, plasma exchange, and corticosteroids, but didn’t mention Soliris. Case reports from Chile and Colombia described successful recovery of kidney function with Soliris.
Due to shortages of Soliris in Brazil, some patients had to stop treatment. In one study, 24 patients had 25 unplanned gaps of 30 days or more, which resulted in 11 episodes of relapse, or a return of aHUS symptoms. The risk of relapse was found to increase over time.
Soliris “is not available on a large scale in many Latin America countries and is often difficult to access, resulting in treatment delays,” the researchers wrote. “Despite these hurdles, patient outcomes have been vastly superior to plasma [exchange].” They said moving to the second-generation [Ultomiris] ravulizumab may help aHUS patients in Latin America “achieve outcomes equivalent to those with [Soliris], but with considerably less administration burden and cost.”
The study was funded by Alexion, AstraZeneca Rare Disease, which markets both Soliris and Ultomiris.
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