Study suggests discontinuing Soliris raises risk of aHUS relapse
Stopping treatment increases likelihood of a relapse by 16.5%
People with atypical hemolytic uremic syndrome (aHUS) who stop taking Soliris (eculizumab) have a 16.5% higher risk of having a relapse, while those who continue treatment have a 76% lower relapse risk, a meta-analysis of published studies suggests.
The differences, however, were only seen in case-control studies, not in cohort studies, which follow patients over time and are considered to be more reliable and of higher quality. This means more evidence is needed to guide which patients can safely discontinue Soliris. Until then, “clinicians should weigh the risks and benefits of continuing therapy on a case-by-case basis, considering all relevant clinical factors including genetic profile, history of relapse, and the potential for adverse events,” the researchers wrote.
The study, “Efficacy of Eculizumab Discontinuation in Atypical Hemolytic Uremic Syndrome: A Systematic Review and Meta-analysis,” was published in Blood Advances.
aHUS is caused by the abnormal activity of the immune system’s complement cascade. In most cases, it’s associated with mutations in genes that regulate the function of the complement cascade.
The treatment landscape for aHUS has improved significantly with terminal complement inhibitors, such as Soliris. Its active ingredient, eculizumab, is an antibody that’s designed to bind to the C5 complement protein, blocking a key step in complement activation.
While Soliris has improved patient outcomes, the need to continue treatment indefinitely raises concerns about its financial burden and adverse effects, especially the risk of meningococcal infections.
Continuing vs. stopping Soliris treatment
Researchers in the U.S. and Canada reviewed studies published up to February that reported on the outcomes of aHUS patients who discontinued versus those who continued treatment to get a better idea about the optimal duration of complement inhibition, the goal being to discern if stopping treatment would increase the risk of a relapse. Thirteen studies, totaling 584 patients, were included. Ten were cohort studies and three were case-control studies.
Continuing Soliris was associated with a 76% lower risk of relapse, the results showed. This reduced relapse risk was tied to the type of study, however, with a significant difference seen only in case-control studies. Considering the absolute risk difference between withdrawing and continuing treatment revealed a 16.5% higher risk of relapse with discontinuing.
No significant differences in relapse rates were seen between those who discontinued or remained on treatment based on specific mutations in complement-related genes. This means “the presence of a particular [mutation] should not guide treatment withdrawal,” the researchers wrote.
The patients were treated for a median of 6.6 months, with follow-ups lasting a median of 27.4 months.
Researchers divided the studies by length of follow-up time — six months, 12 months, 18 months, three years, and five years — but no significant differences were seen in relapse rates based on how long someone was followed, meaning a specific time wasn’t identified when it would be safe and beneficial to stop treatment.
Soliris was generally tolerated well. The most common adverse effects were infections, especially meningococcal infections. These were effectively managed in most cases, however, and patients were able to continue treatment without serious long-term problems.
The lack of randomized controlled clinical trials and uniform standardized outcome measures across all the studies were recognized as key limitations in the analyses. Despite these limitations, the study showcases “the potential for discontinuation in select patients, … but also underscores the need for careful monitoring and individualized decision making,” the researchers wrote.
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