The Risk of ARIA in Monoclonal Antibody Treatments

Monoclonal antibody treatments for Alzheimer’s disease have shown promise in slowing cognitive decline, but they come with a notable risk: ARIA, or Amyloid-Related Imaging Abnormalities. Let’s break down what ARIA is and why it’s a concern for patients and doctors.

ARIA is a side effect that can occur in patients receiving monoclonal antibody treatments like Leqembi (lecanemab). It involves changes in the brain that can be seen on MRI scans. There are two main types of ARIA:

1. ARIA-E: This refers to brain swelling or fluid buildup.
2. ARIA-H: This involves small bleeds in the brain.

The risk of developing ARIA varies among patients. In clinical trials for Leqembi, about 21% of patients experienced some form of ARIA[1]. Most cases of ARIA occur early in treatment, often within the first few months.

Importantly, not all cases of ARIA cause noticeable symptoms. In fact, many patients with ARIA on their scans feel completely normal. When symptoms do occur, they can include headache, confusion, dizziness, vision changes, and nausea[1].

Several factors can increase a person’s risk of developing ARIA:

Genetics play a significant role. People who carry two copies of the APOE ε4 gene, which is associated with increased Alzheimer’s risk, are more likely to experience ARIA. In the Leqembi trial, 45% of patients with two APOE ε4 copies developed ARIA, compared to only 13% of non-carriers[1].

Pre-existing brain changes can also increase risk. Patients with signs of cerebral amyloid angiopathy (CAA), a condition where amyloid builds up in brain blood vessels, may be more susceptible to ARIA[1].

The use of blood-thinning medications might increase the risk of brain bleeds related to ARIA. While the Leqembi trial didn’t show a clear increase in risk for patients on these medications, many doctors are cautious about prescribing monoclonal antibodies to patients taking blood thinners[2].

Managing ARIA risk is an important part of treatment. Doctors typically monitor patients closely with regular MRI scans, especially early in treatment. If severe ARIA is detected, treatment may be paused or stopped. In some cases, medications to reduce brain swelling might be used[1].

Due to these risks, not all patients with early Alzheimer’s disease are eligible for monoclonal antibody treatments. Doctors carefully consider each patient’s individual risk factors before recommending treatment[9].

It’s worth noting that as research continues, scientists are working on ways to reduce ARIA risk. This might involve adjusting drug doses, developing new antibodies that are less likely to cause ARIA, or finding better ways to predict which patients are at highest risk[9].

In conclusion, while ARIA is a significant concern with monoclonal antibody treatments for Alzheimer’s disease, many patients and doctors feel the potential benefits outweigh the risks, especially given the lack of other effective treatments for this devastating disease. As with any medical treatment, the decision to use these drugs should be made carefully, considering each patient’s individual circumstances and in close consultation with healthcare providers.