Discontinuing aHUS treatment may be safe, but requires ‘complex’ decision: Study
Health status, preferences, access to monitoring, follow-up must be considered
It may be safe for some adults with atypical hemolytic uremic syndrome (aHUS) to discontinue treatment once they’re clinically stable, but a decision depends on a complex group of factors, a study based on interviews with aHUS experts indicates.
The patient’s health status, personal preferences, and access to close monitoring and follow-up are among the factors that must be considered.
“aHUS treatment protocols are changing globally in response to new clinical evidence,” wrote the researchers, who said their study “provides compelling evidence on the complexity of factors influencing treatment discontinuation decisions in aHUS, as well as the financial and health consequences of early discontinuation.”
The study, “Treatment discontinuation in adults with atypical hemolytic uremic syndrome (aHUS): a qualitative study of international experts’ perspectives with associated cost-consequence analysis,” was published in BMC Nephrology.
aHUS is a rare form of thrombotic microangiopathy (TMA), a group of diseases where blood clots in small blood vessels damage internal organs, especially the kidneys. In aHUS, this damage is caused by an immune system signaling cascade called the complement system becoming overly active.
Lifelong treatment with agents that block the activity of C5, an important complement cascade protein, are the current standard of care. These include Soliris (eculizumab) and its biosimilars, along with the longer-acting Ultomiris (ravalizumab). Both are administered via infusions directly into the bloodstream. Despite effectively preventing disease activity, long-term use of C5 blockers is costly and necessitates lifelong infusions. They’re also associated with an increased risk of infection.
Research suggests that as long as patients are monitored regularly for kidney disease recurrence, many can safely stop treatment once their disease is under control.
Weighing a decision to discontinue aHUS treatment
To offer more perspective on this issue, a team of international researchers interviewed 10 adult aHUS treatment experts in the U.S., Canada, and Europe between January and December 2023.
This “qualitative study is the first to systematically explore the complexity of factors influencing treatment discontinuation decisions in adult patients with aHUS,” the researchers wrote.
The experts addressed four themes: concerns and prior experience; high-risk vs. low-risk groups; patient preference and adherence; and funding for monitoring and retreatment.
Most experts favored discontinuing treatment for adults if certain clinical criteria were met, such as improved kidney function or a known disease trigger, such as pregnancy, resolving. They mainly cited costs, infusion burden, and potential side effects as reasons for stopping treatment.
“I think that carrying on treatment indefinitely, blindly in all patients, is to the detriment of a significant proportion of patients because of the burden and risk of treatment,” a physician in the U.K. said.
Some experts did favor keeping patients on treatment indefinitely and based that opinion on negative experiences with taking patients off the therapies. The experts generally agreed the decision to discontinue treatment depends on a number of clinical factors, including kidney function improvements, age, and disease severity at symptom onset, genetics, and the chronic kidney disease stage.
All said the patients’ own preference was important. For example, older patients or those with more aggressive disease might hesitate about stopping therapy.
They also agreed that discontinuing treatment should depend on patients’ willingness and ability to adhere to very close monitoring, and to having immediate access to treatment in the event of a relapse. Getting patient monitoring funded while off treatment, along with retreatment, can be challenging, they said.
“If we are making a decision to stop somebody, and therefore taking clinical responsibility for that decision, we need to be able to monitor that patient adequately,” a physician in the U.K. said.
Risks of continuing, stopping treatment
From the interviews, the researchers developed a treatment decision tree and used it to estimate the potential risks of continuing and stopping treatment.
The analysis predicted 21% of patients will have to restart treatment in the first year after a discontinuation. Those stopping treatment will be twice as likely to have a relapse that would resolve without long-term kidney injury as those continuing treatment (8% vs. 4%).
While the risk of a disease relapse resulting in kidney damage should remain low when treatment is stopped (1%), it doubles in a scenario where patients adhere poorly to self-monitoring and detecting a relapse is delayed. The researchers noted that, while the risk of disease activity rises off treatment, “with close attention to self-monitoring, re-initiation of anti-complement therapy can resolve the TMA with very little risk of long-term kidney damage.”
Discontinuing treatment for some patients could have a significant financial impact, the decision-tree analysis showed. While the model was limited to a year, “any lifelong model would predict many millions of dollars-worth of financial savings … with a similar annual risk of adverse events,” the researchers wrote.
Because how aHUS presents and the response to treatment can be different between adults and children, “a parallel investigation of treatment duration decisions among pediatric aHUS experts would be valuable,” the researchers wrote.
The study was funded by Alexion Pharmaceuticals, the original developer of Soliris and Ultomiris, which is now a part of AstraZeneca under the name of Alexion, AstraZeneca Rare Disease.
About the Author
