Complement inhibitors show edge over plasma at stopping aHUS relapses
While both treatments are safe, researchers recommend inhibitors for children
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Complement inhibitors and plasma exchange therapy are equally safe and effective for atypical hemolytic uremic syndrome (aHUS), but complement inhibitors like Soliris (eculizumab) and Ultomiris (ravulizumab-cwvz) offer an edge in preventing relapses, especially in children, according to a new pooled analysis of real-world data.
The analysis reveals that while both treatments successfully manage the rare immune-driven disease, children treated with complement inhibitors see better kidney function and higher survival rates.
Researchers at Taipei Medical University, in Taiwan, evaluated 106 observational studies to help doctors make more informed decisions, especially in resource-limited settings where access to treatment varies. Plasma exchange works by swapping blood plasma to filter out disease-driving proteins, whereas complement inhibitors shut down the overactive immune response that triggers internal clotting and kidney failure.
Despite similar overall success rates, patients undergoing plasma therapy were much more likely to experience disease recurrence.
In children with aHUS, complement inhibitors, therapeutic agents that block the complement cascade, showed a clear advantage over plasma therapy, including fewer relapses, better kidney function, and improved survival.
“Our results indicate that… [plasma therapy] is associated with a higher rate of relapse,” researchers noted, suggesting that complement-blocking therapies should remain the preferred choice for pediatric care.
The study, “Comparison between effectiveness and safety of plasma therapy and complement inhibitors for the treatment of atypical hemolytic uremic syndrome: a systematic review and meta-analysis of real-world data,” was published in Pediatric Nephrology.
A breakdown of hematological and kidney remission
In aHUS, the abnormal activation of the complement cascade — a group of immune proteins that normally help eliminate invaders — drives the formation of blood clots inside small blood vessels.
Symptoms include hemolytic anemia (red blood cell destruction), thrombocytopenia (low levels of platelets that help blood clot), and acute kidney failure. While most patients carry genetic mutations, the disease is often triggered by an infection or, more rarely, self-reactive antibodies, including those directed against complement factor H, a protein that limits the activity of the complement system.
In developed regions, complement inhibitors are typically recommended as first-line treatment. However, in resource-limited settings, plasma therapy is often the primary or only option. To compare these two types of treatment, the research team analyzed diverse participant populations, including children, pregnant women, and kidney transplant recipients.
Comparing remission rates and kidney recovery
The study found that the proportion of patients achieving hematological remission was similar between the complement inhibitor and plasma therapy groups (78.5% vs. 70.2%). The highest success rates were observed with complement inhibitors used alone (92.8%) or in combination with plasma therapy (89.1%), compared with 70.2% with plasma therapy alone.
Kidney disease remission outcomes were also comparable overall (64.0% for inhibitors vs. 59.8% for plasma). However, age played a major role: children fared better with complement inhibitors (74.4%), while adults showed higher remission rates with plasma therapy (73.3%). Notably, in patients with anti-complement factor H antibodies, inhibitors increased the likelihood of kidney recovery by more than two-fold.
Relapse analysis revealed the most striking differences. Almost no patients on complement inhibitors relapsed (0.0% to 1.2%), compared with 15.5% of those on plasma therapy. This gap was particularly wide among children, where the relapse rate for plasma therapy reached 25.5%.
Long-term kidney health followed a similar trend. Less than half as many children treated with complement inhibitors developed chronic kidney disease compared to those on plasma therapy (24.6% vs. 56.6%). Overall death rates were low for both groups, but in the pediatric population, the death rate was significantly lower for those receiving inhibitors (0.3% vs. 7.6%).
Side effects occurred at similar rates for both treatments (27.6% vs. 31.9%). Serious infections were the most common risk with complement inhibitors. In contrast, plasma therapy was more frequently linked to chills, gastrointestinal symptoms, or allergic reactions, with occasional severe reactions like low blood pressure or bleeding.
The researchers concluded that while the overall safety profiles are similar, the higher relapse rates associated with plasma therapy may make complement inhibitors the preferred therapeutic option for pediatric patients.
