A June 17 article in the Los Angeles Times highlighted an important safety risk associated with the new class of medications recently approved for treating Alzheimer’s disease. The drugs are anti-amyloid monoclonal antibodies and include aducanumab, donanemab, and lecanemab. Of these, only lecanemab has achieved full FDA approval at the time of writing. The side effects are collectively known as amyloid-related imaging abnormalities, or ARIA, and are potential side effects for each of these drugs, though with differential frequencies observed across the clinical trials of these medications. The specific drug side effects include what are often referred to as bleeding and swelling in the brain (mainly microhemorrhages [ARIA-H] and vasogenic edema [ARIA-H], respectively). The article highlighted the importance of these potential side effects, emphasizing a few rare cases that were in fact fatal.
What was largely missing from the article was a balanced review of lecanemab and other anti-amyloid monoclonal antibodies, which are the product of decades of research progress and are the first ever approved treatments that directly target the biology of Alzheimer’s disease. Around 13% of patients treated with lecanemab in a large phase 3 clinical trial experienced ARIA-E, though the risk was higher in patients of particular genotypes. Most cases of ARIA do not cause symptoms and therefore require routine imaging to be detected (and thus accounted for the naming of the of the phenomenon).
The article suggested that some patients eligible for treatment on the basis of having a diagnosis of Mild Cognitive Impairment, or MCI, are not likely to progress to dementia and may even improve without treatment. In fact, anti-amyloid monoclonal antibodies are only appropriate for use in patients with MCI after Alzheimer’s disease has been determined to be a cause of their cognitive problems. These individuals are at much greater risk for progression to dementia, compared to patients with MCI who do not have Alzheimer’s disease, and are unlikely to improve in their cognitive problems.
The article downplayed the efficacy of these treatments, noting that patients and families wouldn’t notice the difference. In fact, the goal with these medications is to slow disease progression, which would be largely imperceptible to patients and families. This is a key point of education when we enroll patients and families in these clinical trials—not noticing a change could be the best sign that the drugs are working.
Are the anti-amyloid monoclonal antibodies a cure? No. Are brain swelling and bleeding important and serious safety concerns? Yes. Do we need more effective, safer, more convenient treatments for people living with Alzheimer’s disease? Most definitely. But to downplay the important progress being made (and made possible by patients and families who volunteer for research) is not in service to the public. Clinicians will provide the education needed for patients and families to make informed decisions about these treatments, including helping them understand the potential risks and the potential benefits.
The media can affect attitudes toward new treatments, toward potential false hope with pseudomedicines, and toward research. Hopefully, this will include helping more people understand the need for public participation to continue research progress toward safer and even more impactful treatments and preventions for Alzheimer’s disease.
