Eli Lilly and Company (NYSE: LLY) and Avid Radiopharmaceuticals, Inc., a wholly owned subsidiary of Lilly, today 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 today 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.
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 percent 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 center after three months, the physician updated the diagnosis and recorded an actual management summary. Patients then returned to the center one year post baseline for assessment of patient and caregiver outcomes including change in cognitive status (ADAS-Cog), health outcomes/resource utilization, 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.
Key Results Details
- The percentage of patients with management changes was higher in the immediate feedback group compared to the delayed feedback group (68.0 percent versus 56.0 percent)
- 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 percent of amyloid positive versus only 27.0 percent 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 percent amyloid positive and 43.0 percent 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 percent in the immediate feedback group compared to 6.4 percent in the delayed feedback group)
- Of note, diagnosis change among cases with contradicting initial diagnosis versus scan results was 85.6 percent for the immediate feedback group compared to 11.9 percent for the delayed feedback group
- There were no group differences in cognitive performance or health outcomes at one year as measured by the following:
- Cognitive change from baseline (ADAS, MMSE, FAQ)
- Resource use on the RUD
- Quality of life on the QoL AD
- Caregiver Self Efficacy
Study limitations included:
- 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 behavior and available treatments. Results could change with physician education and experience with amyloid PET scans, and with the advent of new medications