Amyloid-related imaging abnormalities
Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.
We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?
Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.
While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.
Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.
Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.
Patients on anticoagulation
Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?
Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.
When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.
A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.