Eli Lilly and Company, a global healthcare leader, and Avid Radiopharmaceuticals, Inc., a wholly owned subsidiary of Lilly, announced new data showing that knowledge of amyloid status as determined by Florbetapir F 18 injection imaging altered diagnosis and management in the majority of patients being studied.
This is the first study to look at the impact of amyloid imaging on diagnosis and actual patient management using a randomized, controlled prospective design. These findings were presented at the Alzheimer's Association International Conference 2015 (AAIC) in Washington, D.C.
The presence of beta-amyloid neuritic plaque in the brain may provide additional information to supplement a physician's clinical assessment of a patient with cognitive impairment. However, a negative beta-amyloid imaging scan indicates sparse to no plaques are currently present, which is inconsistent with a neuropathological diagnosis of Alzheimer's disease and reduces the likelihood that a patient's cognitive impairment is due to the disease. It is important to note that errors may occur during image interpretation. Also, a positive scan does not establish a diagnosis of Alzheimer's disease or other cognitive disorders and a negative scan does not preclude the development of brain amyloid in the future.
"These study results are the first to suggest in a controlled study that adding florbetapir to the diagnostic evaluation changed actual patient diagnosis and management by physicians who regularly manage this complicated and devastating disease," said Michael Pontecorvo, Ph.D., vice president, clinical development, Avid Radiopharmaceuticals, a wholly owned subsidiary of Lilly.
"Alzheimer's disease is one of many possible causes of cognitive impairment, which can make diagnosis challenging. These findings provide further support for how knowledge of the presence or absence of amyloid pathology may affect both diagnosis and management in patients being evaluated for Alzheimer's disease or other possible causes of cognitive decline."
In addition to altering patient diagnosis, results showed that knowledge of amyloid status as determined by florbetapir imaging changed patient management in the majority of study patients, particularly Alzheimer's disease medications (cholinesterase inhibitor use), in a direction consistent with amyloid status. The researchers found no group differences in cognitive performance or health outcomes at one year, and changes in medical history, psychotropic drug use, and psychiatric-related events were not significantly different between the immediate and delayed feedback groups. There was no evidence of increased safety risk associated with early disclosure of amyloid status.1
These data add to a growing body of work that suggests knowledge of amyloid status may change intended and actual patient management.
The goal of this multicenter study was to evaluate the impact of amyloid positron emission tomography (PET) on patient management and outcomes in a randomized, controlled setting. After identifying patients seeking diagnosis for mild impairment or dementia, where Alzheimer's disease was considered a possible cause ( < 85 per cent certain), physicians recorded a working diagnosis and management plan. Patients underwent a florbetapir PET scan and were then randomized to either immediate or delayed (one year) feedback groups regarding amyloid status.
When patients returned to the centre after three months, the physician updated the diagnosis and recorded an actual management summary. Patients then returned to the centre one year post baseline for assessment of patient and caregiver outcomes including change in cognitive status (ADAS-Cog), health outcomes/resource utilisation, mood, function and quality of life. The pre-specified primary analyses examined the impact of immediate feedback versus delayed feedback of amyloid status on diagnosis and management changes at three months.
A total of 618 subjects were randomized to the immediate (308) or to the delayed (310) amyloid PET feedback arms, including 174 subjects in France, 221 in Italy and 223 in the United States. Six hundred and two subjects completed the three month and 560 completed the one year follow-up visits.
The percentage of patients with management changes was higher in the immediate feedback group compared to the delayed feedback group (68.0 per cent versus 56.0 per cent). This difference was driven mainly by Alzheimer's disease medication changes, particularly cholinesterase inhibitor use, when patients were sorted by amyloid status. In the immediate feedback group, cholinesterase inhibitor use increased in amyloid positive subjects and decreased in amyloid negative subjects so that 67.0 per cent of amyloid positive versus only 27.0 per cent of amyloid negative subjects were receiving medications three months after scan.
In contrast, in the delayed feedback group, Alzheimer's disease medication use increased regardless of amyloid status such that 56.0 per cent amyloid positive and 43.0 per cent amyloid negative subjects were receiving cholinesterase inhibitors. Results suggested that knowledge of amyloid status as determined by florbetapir imaging changed actual patient diagnosis (32.6 per cent in the immediate feedback group compared to 6.4 per cent in the delayed feedback group). Of note, diagnosis change among cases with contradicting initial diagnosis versus scan results was 85.6 per cent for the immediate feedback group compared to 11.9 per cent for the delayed feedback group
There were no group differences in cognitive performance or health outcomes at one year as measured by the cognitive change from baseline (ADAS, MMSE, FAQ), resource use on the RUD, quality of life on the QoL AD, caregiver self efficacy.
Physicians frequently failed to perform the diagnostic and neuropsychology tests and follow-up visits that were a part of their pre-scan management plan. The study was not designed to assess health outcomes impact. The trial reflects current physician behaviour and available treatments. Results could change with physician education and experience with amyloid PET scans, and with the advent of new medications.
Amyvid is a radioactive diagnostic agent for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) and other causes of cognitive decline.
A negative Amyvid scan indicates sparse to no neuritic plaques and is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition; a negative scan result reduces the likelihood that a patient's cognitive impairment is due to AD. A positive Amyvid scan indicates moderate to frequent amyloid neuritic plaques; neuropathological examination has shown this amount of amyloid neuritic plaque is present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as older people with normal cognition. Amyvid is an adjunct to other diagnostic evaluations.
A positive Amyvid scan does not establish a diagnosis of AD or other cognitive disorder. Safety and effectiveness of Amyvid have not been established for predicting development of dementia or other neurologic condition, monitoring responses to therapies.
Amyvid for intravenous use is supplied in 10 mL, 30 mL, or 50 mL multidose vials containing 500-1900 MBq/mL Florbetapir F 18.
The most common adverse reactions reported in clinical trials were headache (1.8 per cent), musculoskeletal pain (0.7 per cent), blood pressure increased (0.7 per cent), nausea (0.7 per cent), fatigue (0.5 per cent), and injection site reaction (0.5 per cent).