Alzheimer's Drug ARIA Monitoring: Real-World Study Results

— Collaboration between prescribers and radiologists is key, lecanemab data show

Rates of amyloid-related imaging abnormalities (ARIA) in Alzheimer's disease patients treated with lecanemab (Leqembi) in the real world were consistent with those seen in clinical trials, data from the LEADER study showed.

Anti-amyloid drugs like lecanemab require MRI monitoring for ARIA, making prescriber-radiologist collaboration essential, said Daryl Rhys Jones, PhD, of drugmaker Eisai in Nutley, New Jersey, at the American Society of Functional Neuroradiologyopens in a new tab or window meeting in Newport Beach, California.

ARIA is a consequence of amyloid in blood vessel walls. Two types of ARIA can emerge after anti-amyloid drug treatment: ARIA with edema or effusion (ARIA-E) or ARIA with hemosiderin or hemorrhage (ARIA-H).

In the real-world LEADER study, ARIA rates appeared to be lower than rates seen in the phase III CLARITY ADopens in a new tab or window trial of lecanemab, though the differences may not be significant:

• Any ARIA: 12.3% vs 21.3%
• ARIA-E: 6.5% vs 12.6%
• ARIA-H: 7.6% vs 17.3%
• Concurrent ARIA-E and ARIA-H: 1.9% vs 8.2%

The median time to ARIA-E was 3.4 months, Jones reported. Results were similar between 1.5T and 3T MRI. "This suggests that the power of MRI is not really making a difference in detection, at least in the real world," he told MedPage Today.

ARIA rates in LEADER were consistent with other real-world evidence, including data from the ALZ-NET registryopens in a new tab or window, he added.

Lecanemab, an antibody directed against aggregated soluble and insoluble forms of amyloid beta, was approved in 2023opens in a new tab or window to treat mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's dementia. The drug carries a boxed warningopens in a new tab or window that ARIA-E or ARIA-H can occur, with a notice that APOE4 homozygotes have a higher incidence of ARIA than heterozygotes and noncarriers.

ARIA is often asymptomatic, and in rare cases, it can be fatal. Lecanemab prescribing information calls for MRI at baseline, then after 1, 2, 3, and 6 months of treatment to monitor for ARIA.

LEADER is an ongoing, multisite, retrospective study that evaluates lecanemab in clinical settings. It incorporates surveys and interviews with healthcare practitioners with chart and electronic medical record data for up to 50 patients per site.

This interim analysis was based on data from 432 patients with early Alzheimer's disease. All participants received at least seven biweekly lecanemab infusions. Some received intravenous (IV) or subcutaneous maintenance treatment after 18 months of IV initiation treatment. Participants had an average of 520.7 days on lecanemab and an average of 25.8 doses.

The LEADER study includes diverse real-world settings, Jones noted. "We didn't just select academic centers that might have extensive experience," he said. "There are general neurologists included in LEADER who were not part of CLARITY AD, so they were treating these patients for the first time. Yet, they were able to implement lecanemab and successfully monitor for the safety of lecanemab in their patients."

Close prescriber-radiologist collaboration was key to that success, Jones observed. This meant establishing communication between neurologists and radiologists -- "not just themselves, but their front staff, who might be involved with scheduling, and the administrative team at the site," he said.

"It is very important ... to ensure that the radiologist understood what was needed, because the neurologist needs to know, OK, there is no ARIA, I can continue with treatment, or OK, there is ARIA, but this is asymptomatic and mild," Jones pointed out. There needs to be "very clear guidance to the neuroradiologist about what they should be describing for the neurologist," he said.

The analysis included 12 LEADER sites, "but we've expanded now to 20 sites and we're expanding our patient numbers as well," Jones noted. "And, importantly, we're now looking at subcutaneous administration," he added, which the FDA approvedopens in a new tab or window earlier this year.