Possible Consequences of the Approval of a Disease-Modifying Therapy for Alzheimer Disease

“While the aducanumab clinical trial data are complicated and the path to approval far from clear, approval is certainly possible, and other promising antibodies (such as Biogen’s BAN-2401 and Genentech’s gantenerumab) are just steps behind. Thus, the long-awaited advent of disease-modifying therapy for AD [Alzheimer disease] may be soon upon us, representing a major advance in the battle against AD and a beacon of much-needed hope for patients.

[..] The approval of aducanumab or any disease-modifying therapy for AD likely will result in a considerable immediate demand for capacity to provide formal diagnoses of AD dementia, including cognitive and AD biomarker testing. This demand may come not only from symptomatic patients who already may have an AD diagnosis, but from the legions of worried-well older adults, many of whom may have subjective memory complaints. According to a recent analysis, this demand could greatly overwhelm the limited capacity of the few academic memory clinics in the country, likely necessitating some primary care clinicians, geriatricians, psychiatrists, and general neurologists with varying levels of training in AD diagnostics to quickly gain expertise in accurately differentiating AD from other disorders, and in navigating the likely complex criteria that will govern eligibility for this new therapy. Initiation of anti-amyloid antibody therapy will likely also be accompanied by requirements for closer clinical follow-up, as well as repeated brain magnetic resonance imaging to assess for amyloid-related imaging abnormalities, including brain edema and microhemorrhage, both known consequences of this class of drug. The increased diagnostic positron emission tomography (PET) imaging and magnetic resonance imaging–based safety monitoring will further tax the imaging infrastructure. The resultant care access issues will almost certainly be magnified among underserved and marginalized populations, which already experience limited access to care and experience higher rates of dementia. Academic memory centers could assist in this area by increasing clinical capacity, expanding training programs for future dementia physicians, and by offering expanded training opportunities for community physicians and outreach programs to underserved communities. Development of clear diagnostic tools that allow nonspecialists to identify eligible patients may be helpful, perhaps in conjunction with dementia screening instruments.

[..] it is very likely that approval of this drug (or others like it) would be accompanied by restrictive criteria for its use only in this segment of patients with AD. As many patients with more progressed symptomatic AD have eagerly awaited the approval of a disease-modifying agent, physicians may face the difficult task of explaining that this newly approved therapy is not available to patients because their disease is too advanced. Moreover, many asymptomatic individuals or those with very mild subjective memory complaints may demand biomarker testing and, if positive, therapy. This could create a complex situation for physicians, which could be made worse if some choose to skirt these guidelines to provide treatment to these 2 groups of patients. Thus, it is critical that eligibility criteria for the use of this new drug be very carefully considered and that the rationale for these criteria be well articulated to the public.

[..] Presumably, the Centers for Medicare & Medicaid Services and private insurers will begin to cover FDA-approved amyloid PET imaging to support an AD diagnosis once a disease-modifying therapy is available. While amyloid PET imaging is a highly valuable biomarker for AD diagnosis, clinical interpretation of this imaging can be complex, as amyloid plaques are present in approximately 30% of the cognitively normal population older than 65 years and can coexist with other neurodegenerative diseases. Thus, amyloid imaging must be accompanied by appropriate clinical evaluation to avoid inaccurate diagnoses and unnecessary therapy.

[..] In an ideal scenario, the therapy would eventually lower health care costs by reducing the need for advanced dementia care. However, the economics could change drastically if the therapy is overprescribed and improperly used, resulting in increased cost with less benefit. Thus, it is critical that dementia experts position themselves as leaders in this conversation, rather than allowing policy to be dictated by lobbying groups with varied interests.”

Full editorial, Musiek ES and Morris JC. JAMA Neurology 2020.11.30