Pauline Anderson

July 22, 2015

WASHINGTON, DC — Knowing the amyloid status of patients could help direct anti-Alzheimer's disease (AD) drugs to those most likely to benefit from them and prevent prescribing these agents unnecessarily, new research suggests.

A new study indicates that physicians with access to positron emission tomography (PET) using florbetapir F18 (Amyvid, Avid Radiopharmaceuticals) changed diagnosis and treatment decisions, particularly use of cholinesterase inhibitors, on the basis of the presence of amyloid on the scan, compared with physicians who did not immediately receive this information.

"Patients deserve to have an accurate diagnosis; they deserve to have the right treatment," Michael Pontecorvo, PhD, vice president, clinical development, Avid Radiopharmaceuticals, a wholly owned subsidiary of Lilly, told Medscape Medical News.

The results were presented here at the Alzheimer's Association International Conference (AAIC) 2015. The study was funded by Avid Radiopharmaceuticals.

Treatment Decisions

In this analysis, researchers wanted to determine how doctors might change their management of patients with cognitive impairment of uncertain cause if they had information from florbetapir PET. This approach detects the presence of β-amyloid neuritic plaque in the brain.

They launched the first — and to date the only — randomized, controlled, multicenter trial to investigate this issue.

Investigators first asked physicians what they thought the diagnosis was for each patient and whether they planned to do more tests, treat the patient, or refer him or her to another specialist.

Patients underwent florbetapir PET and then were randomly assigned to an immediate (n = 308) or a 1-year delayed (n = 310) amyloid status feedback group.

After 3 months, the physicians were asked again about their diagnosis and whether they would change any of the three management components. Researchers also determined what the actual management strategy was for each patient.

About two thirds of patients (68%) with immediate PET information had a change in one of the management components. About 56% of patients with delayed neuroimaging information had some management change.

The biggest impact of having amyloid information was on treatment decisions, said Dr Pontecorvo. "If patients were amyloid positive, they tended to get a cholinesterase inhibitor; if they were amyloid negative, they tended to have it taken away."

At the end of 3 months, 67% of amyloid-positive patients and 27% of amyloid-negative patients in the immediate-feedback group were receiving treatment compared with about 50% of the patients in the delayed-feedback group.

So there was a movement in the direction of appropriate treatment that was indicated by the scan, which is important, said Dr Pontecorvo. "Knowing amyloid status changed the way physicians treated their patient; it changed their use of AD medications in a direction consistent with the amyloid status."

The change in medication based on the scan persisted for up to a year.

Having the amyloid status changed the actual patient diagnosis in 32.6% of cases in the immediate-feedback group compared to 6.4% in the delayed-feedback group.

Knowing a patient's amyloid status made treating physicians "more confident," noted Dr Pontecorvo.

"We hope that physicians will move to a point of seeking diagnosis at the first sign of patient complaint," said Dr Pontecorvo. "But where this test fits in the algorithm depends, I think, on what other tests the physician has done and what the patient's presentation looks like."

The test should "certainly not be used in patients who are clinically normal," he added. "It's for people who are seeking diagnosis, who have an impairment."

Provides "Clarity"

Commenting on the study for Medscape Medical News, James Hendrix, PhD, director, Global Science initiatives, Alzheimer's Association, emphasized that PET should be used only when the diagnosis is unclear and should adhere to the appropriate use criteria that were developed by the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging.

According to these criteria, amyloid PET may have greatest value in patients with progressive, unexplained mild cognitive impairment; dementia of uncertain cause due to atypical or mixed symptoms; or unusually early age of onset.

In appropriate cases, a PET scan can provide "clarity" surrounding a diagnosis, but it can also rule out AD, which could have "a huge impact," said Dr Hendrix. "The clinician then needs to go further to try to understand what else could be the cause. So ruling it in is useful, but ruling it out could be powerful too."

PET scans can also facilitate the appropriate use of cholinesterase inhibitors, said Dr Hendrix. For example, he said, such drugs can make matters worse in patients with frontotemporal dementia. "If your clinician doesn't know or isn't sure, he or she may put someone on that drug and they may decline rapidly; that's not good for anyone."

The study uncovered no evidence that having a PET scan caused psychological problems for patients, said Dr Pontecorvo. In those who got the information, there was no difference in psychiatric events, such as depression and anxiety, or in psychiatric medication use.

"This is very important message for families and for clinicians," commented Dr Hendrix, "One of the reasons clinicians may be reluctant to tell people (about the diagnosis) is that they don't want to stress them, but the message from this study is that a clear diagnosis actually helps people because they can plan. Just because there is no disease-modifying therapy doesn't mean that you shouldn't be told" the results of an amyloid scan.

The researchers also looked at 1-year outcomes of cognition (using the Alzheimer's Disease Assessment Scale cognitive subscale) and health, but didn't note any between-group differences, according to Dr Pontecorvo. "It's a very small study for evaluating those things."

He considers this research as a sort of "pilot" study leading up to another study, the 4-year Imaging Dementia–Evidence for Amyloid Scanning (IDEAS) trial, that will be launched in January 2016. The Alzheimer`s Association is contributing funding for the study, which will enroll 18,488 Medicare beneficiaries aged 65 years and older over a period of 24 months.

These participants will be recruited into one of two subgroups: (1) progressive unexplained mild cognitive impairment and (2) dementia of uncertain cause.

IDEAS researchers will aim to assess the effect of amyloid PET on the management of study participants and on outcomes such as hospital admissions and emergency department visits.

The IDEAS study was developed in response to the 2013 Centers for Medicare & Medicaid Services (CMS) National Coverage Decision on amyloid PET in dementia and neurodegenerative disease, in which CMS decided to cover brain amyloid imaging only under "Coverage with Evidence Development." CMS questioned the ability of amyloid PET to lead to improved health outcomes. Under the on amyloid PET in dementia and neurodegenerative, Medicare will provide coverage for one amyloid PET scan per patient enrolled in an approved clinical study.

Avid Radiopharmaceuticals funded the study. Dr Pontecorvo is an employee of Avid Radiopharmaceuticals. Dr Hendrix has disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2015. Oral session DT-02-03. Presented July 22, 2015.

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