Most people with atypical hemolytic uremic syndrome (aHUS) whose disease is in remission after treatment with complement-inhibiting medications like Soliris (eculizumab) can safely stop the therapy with close monitoring, a small study suggests.
These findings were reported in “Outcomes of a clinician-directed protocol for discontinuation of complement inhibition therapy in atypical hemolytic uremic syndrome,” published in the journal Blood Advances.
aHUS is caused by the abnormal activation of part of the immune system, known as the complement cascade. This leads to inflammation that damages blood vessels, especially those in the kidneys.
Soliris and Ultomiris (ravulizumab), developed and marketed by Alexion, are currently considered standard-of-care treatments for aHUS. Both medications work by blocking the activity of the C5 protein, which is part of the complement cascade. The main difference between the two is that Ultomiris, a newer medication, is more stable and lasts longer in the body, so it needs to be administered less frequently — every two months, as opposed to every two weeks with Soliris.
At present, treatment with these complement-inhibiting medications is meant to be lifelong. However, their long-term use is expensive and can raise the risk of certain infections. The need for regular infusions can also be burdensome to patients.
As such, researchers are exploring whether these treatments can safely be discontinued by certain individuals under specific circumstances.
A team led by researchers at Johns Hopkins University analyzed clinical data on 31 people with aHUS who were treated with Soliris between 2014 and 2020.
Most patients were women (77.4%), with a median age of 44 at diagnosis. None of the patients had undergone a kidney transplant, and all were followed for at least three months.
Of these 31 people, 18 discontinued treatment under a physician-supervised protocol. In order to be eligible for discontinuation under this protocol, patients had to have stable kidney function and no clinical evidence of disease activity, among other requirements.
Seven other patients stopped using Soliris on their own, a status called nonadherence or the failure to take medication as instructed.
Among patients who stopped treatment under the physician-supervised protocol, two (11.1%) later relapsed, as did three (42.9%) of the seven who discontinued due to nonadherence.
Of these five relapse patients, four were successfully re-treated with Soliris, without losing kidney function in the long-term. The fifth person died after being admitted to the emergency room due to aHUS- and blood pressure-related health problems.
Statistical analyses found that nonadherent patients were more than eight times more likely to relapse, which was considered to be statistically significant.
Other factors, such as the presence of aHUS-associated genetic mutations or of clear disease triggers, were not significantly associated with relapse risk. The researchers noted, however, that these statistical analyses were limited by the study’s relatively small sample size.
Among the 25 total patients who discontinued Soliris, nine saw their kidney function improve since stopping treatment, and 15 saw it stabilize. Kidney function decline was observed in one patient after treatment interruption.
“We show that for most aHUS patients, discontinuation of [complement] inhibitor [Soliris] therapy is safe and acceptable without loss in renal function when done under close monitoring to allow early detection and treatment of relapses,” the researchers concluded.
The team noted that these findings are from a small set of patients followed at a single center. As such, they stressed the need for larger and multisite studies to better determine the “renal and vascular safety of limited duration eculizumab [Soliris] therapy.”
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