Soliris withdrawal possible in aHUS with careful monitoring: Study
Stopping treatment could ease patient burden, save healthcare system money
Most people with atypical hemolytic uremic syndrome (aHUS) who are stable on Soliris (eculizumab) can stop treatment after at least six months without having a relapse, provided that they’re carefully monitored, a recent study reported.
Scientists expect that this could prevent treatment-related complications and burden for patients, while also saving the healthcare system money.
“Our findings are exciting as they have the potential to significantly change the way we manage aHUS, and this may be life-changing for some patients,” Neil Sheerin, PhD, professor at Newcastle University, consultant physician for the Newcastle Upon Tyne Hospitals NHS Foundation Trust, and the study’s senior author, said in a university news story.
According to Sheerin, this new treatment approach is expected to save the U.K.’s publicly funded healthcare system £110.4 million (nearly $150 million) over five years.
The study, “Eculizumab withdrawal and monitoring in atypical haemolytic uraemic syndrome (SETS aHUS): a multicentre, open label, prospective, single arm trial,” was published in The Lancet Regional Health Europe. It was funded by the U.K.’s National Institute for Health and Care Research.
Study evaluates whether Soliris can be halted once aHUS is under control
In aHUS, blood clots form in small blood vessels due to the abnormal activity of the immune system’s complement cascade. These clots cause organ damage, especially in the kidneys.
Eculizumab, the active ingredient in Soliris, is an antibody designed to bind to the C5 complement protein, ultimately blocking a key step in complement activation. This should prevent clotting in small blood vessels, thereby helping to control aHUS.
Soliris is approved for children and adults with aHUS in the U.S., U.K., and elsewhere. The brand-name medication is marketed by AstraZeneca, but functionally equivalent biosimilars are also available.
Upon the treatment’s initial regulatory approvals for aHUS, it was recommended that most individuals stay on Soliris for the rest of their lives. Treatment involves infusions given intravenously, or directly into the bloodstream, every other week.
While effective, Soliris comes with potentially serious side effects, including an increased risk of life-threatening meningococcal infections. It also burdens patients with the need for regular infusions.
This prompted scientists to start evaluating whether there was a more optimal duration of treatment, and if Soliris can be discontinued once aHUS is under control.
That was the goal of the open-label SETS aHUS trial, conducted across 15 hospitals in the U.K. It enrolled 28 people with aHUS who were older than 2. All had been on Soliris for at least six months, with the median being nearly two years, and all were in remission.
Each participant discontinued treatment and was carefully monitored for disease activity over a two-year follow-up period.
Relapse rate was 14.3% over the two-year follow-up period
The main goal was to evaluate how many participants experienced harm due to an aHUS relapse after stopping treatment with Soliris. Harm was defined as irreversible kidney function decline, an episode of acute kidney injury that required treatment to replace the function of the failing kidneys, or a non-kidney complication that required hospitalization or led to irreversible organ damage or death.
Overall, one adult (3.6%) experienced such harm, characterized by a gradual decline in kidney function. The participant was restarted on Soliris nearly 1.5 years after initially discontinuing it, but kidney function did not recover.
Three other people — one adult and two children — experienced a disease relapse in the first six months after stopping Soliris, but were able to restart treatment without any evidence of permanent harm.
Initially, I was told eculizumab [Soliris] would be a lifelong commitment, which felt very daunting. But this amazing research has shown the treatment can successfully be withdrawn and that’s fantastic
Considering all four of these individuals, the overall relapse rate was 14.3% over the two-year follow-up period. That amounts to one relapse every 14 years off treatment across the whole group of participants, according to the authors.
“We show that … withdrawal of eculizumab [Soliris] can be achieved without exposing patients to additional harm compared with continued treatment,” the researchers wrote.
Louise Percival, a 35-year-old who was diagnosed with aHUS in 2017, was among the trial participants who has not experienced any disease relapse since stopping Soliris. Percival, who indicated that regular treatment infusions had been substantially impacting her life quality, said she now feels like herself again.
“Initially, I was told eculizumab [Soliris] would be a lifelong commitment, which felt very daunting,” Percival said. “But this amazing research has shown the treatment can successfully be withdrawn and that’s fantastic.”
Now, all trial participants will continue to be monitored closely.
“This will allow us to answer important questions, such as can people withdraw again from eculizumab [Soliris] once they’ve relapsed, and can we predict more accurately which people will have a relapse following treatment withdrawal,” Sheerin said.
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