Review Confirms Soliris Effective Against aHUS-related Kidney Disease in Children
Kidney function biomarkers either improved or normalized with the treatment
Researchers suggested that more research is necessary, however, to establish its effectiveness, safety, and time of discontinuation in the long term.
The review study, “The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review,” was published in Pediatric Nephrology.
In aHUS, abnormal activity of the complement cascade — part of the immune system that helps defend the body against invading microbes — triggers blood clots to form in small blood vessels. These clots damage internal organs, especially the kidneys. In fact, about half of children with aHUS progress to late-stage chronic kidney disease.
Soliris was the first approved treatment for aHUS. It works by blocking the action of C5, one of the many proteins of the complement cascade. However, there are no systematic reviews of published studies evaluating the effectiveness and safety of Soliris in children with aHUS.
Soliris for childhood chronic kidney disease
The aim of this study, by researchers at the Federal University of Minas Gerais, Brazil, was to review the current literature to determine if Soliris safely reduced chronic kidney disease in children with aHUS.
The team searched medical databases for clinical trials and observational studies that included children with aHUS treated with Soliris. Case reports, review articles, animal studies, and studies about kidney transplants were excluded from the analysis.
From the 15 studies that met the inclusion criteria, 10 were cohort studies — a type of longitudinal study that follows participants over a time period. Four were case series and one was a clinical trial. A few studies included adults, but only data from participants up to age 18 were extracted.
In the overall population, children mean age ranged up to nearly 8 years, and up to 60% were female. In those treated with Soliris, up to 70% were female and mean age ranged up to 7 years.
In most studies, outcomes of those treated with Soliris were favorable, with improvements in blood-based and kidney function measures. Biomarkers for kidney function, including creatinine levels and the estimated glomerular filtration rate, either improved or were normalized.
The single clinical trial included in the analysis was an open-label Phase 2 trial (NCT01193348) that assessed the safety and effectiveness of Soliris in 22 aHUS children, ages 1 month to 18 years.
The study reported the majority of treated participants had an improvement in kidney function, and 64% demonstrated a complete recovery — defined by a complete normalization of blood parameters accompanied by an improvement in kidney function — after 26 weeks (six months). Those who didn’t achieve a complete recovery had worse kidney function at the study’s start.
Side effects, mostly mild or moderate, occurred in 20 children and included fever, cough, abdominal pain, diarrhea, and upper respiratory tract infection. Although three events were deemed severe, none were attributed to Soliris.
Only two studies reported a lack of statistical significance related to the clinical outcomes of children treated with Soliris. One study reported no significant differences in kidney function between short- and long-term Soliris-treated groups. The authors noted that their findings “should be interpreted with care due to the small sample size.”
One study reported an allergic reaction in one patient and convulsions and sepsis in another. In another study, 25% of participants had bacterial infections, 12.5% had viral infections, and 20.8% had non-infectious side effects. However, it was not possible to determine if these were related to Soliris or due to previous health conditions as patients often underwent dialysis or other invasive procedures that were expected to increase the risk of infections.
In a study that focused on safety, a higher proportion of treated patients reported serious infections, including one meningococcal infection, which was resolved. Six patients died, of whom four had been receiving Soliris. Researchers noted that treated patients had more severe disease at the study’s start. Three other studies reported deaths, but all were due to causes unrelated to Soliris.
Soliris was stopped in one case series in those with stable disease who were showing no signs of thrombotic microangiopathy (TMA) — a group of conditions that also includes aHUS and are characterized by red blood cell destruction, low platelet counts, and organ damage driven by blood clot formation in small blood vessels. One patient relapsed one year later and further Soliris treatment led to complete remission with no additional treatment.
“Overall, [Soliris] seems a very effective and safe drug to treat aHUS in pediatric patients, especially considering the disease outcome before the availability of [Soliris],” the researchers wrote. “However, more robust and high-quality evidence is needed to better establish the duration of treatment and safe discontinuation, as well as long-term efficacy and safety.”