UB geriatrician: ‘Unequivocal enthusiasm for the FDA’s action on aducanumab might not be in the best interests of patients’

BUFFALO, N.Y. – Patients with Alzheimer’s disease and their families may be understandably enthusiastic about the Food and Administration’s recent approval of aducanumab, but a University at Buffalo expert in geriatrics cautions against unequivocal enthusiasm for the drug.

“No doubt we all are eager to have disease-modifying treatments for Alzheimer’s disease and other dementias,” says Bruce Troen, MD, chief of the Division of Geriatrics and Palliative Medicine in the Department of Medicine at the Jacobs School of Medicine and Biomedical Sciences and director of the Center of Excellence for Alzheimer’s Disease at UB. “Indeed, many families are desperately eager for any treatment that might mitigate the disease.”

But, he notes, “unequivocal enthusiasm for the FDA’s action on aducanumab might not be in the best interests of patients.”

Limited clinical trials, unclear results, Troen says

Among the issues with aducanumab that Troen says have been cited by the American Geriatrics Society include incomplete and ambiguous findings from the drug’s two clinical trials, both of which were stopped half-way through and for which only one may have shown benefit in a statistical analysis of the data. “The research from that trial has not been published in a peer-reviewed journal,” he says. “The data also do not address whether the results are generalizable to all older adults without exacerbating health disparities.”

Troen, who is also a physician with UBMD Internal Medicine, says that it remains unclear as to whether the drug provides a benefit for the majority of Alzheimer’s patients. Participants in the trial had either mild cognitive impairment or mild Alzheimer’s disease. The American Geriatrics Society concluded that the clinical significance of any possible improvement was not clear. Troen also points out that those with moderate and advanced dementia were not enrolled in the trial.

“Even with accepted medications for Alzheimer’s, the benefit at best is modest,” Troen says. “My approach is to look for non-pharmacological solutions as much as possible. And for the behavioral and psychological symptoms associated with dementia — particularly in advanced cases, there’s abundant evidence that non-pharmacological approaches are superior and that existing pharmacological approaches can even be detrimental.

A holistic approach is the geriatrics perspective, he says

“People say that there is no treatment for Alzheimer’s disease and dementia,” says Troen. “The fact is, we do treat patients. Although at this time we do not have disease-modifying approaches, we do our best to maintain as much as possible the quality of life for the patient. The geriatrics perspective is to bring a holistic approach to the individual, to marshal an interdisciplinary team with the best supportive environment, appropriate family support and social services in addition to providing the best possible medical care in order to mitigate the impact of comorbidities.”

He notes that just like hypertension, Alzheimer’s and dementia cannot be cured, but they can be well-managed.

“Health care providers are always eager to treat a disease, and we know how desperately eager families are to have something that might benefit the patient,” he continues. “Because this may not be that drug, I’m really concerned that there’ll be a rush, nevertheless, to prescribe the drug, but that they will find that it’s not going to yield major improvements.”

Troubling side effects, worry over future clinical trials

Troen notes that, as with any drug, there are side effects. In one of the trials, the higher dose was accompanied by potentially serious side effects of brain swelling and brain hemorrhages in one third and one fifth of the participants, respectively. In addition, there are no clear guidelines about which patients should be considered for treatment, how they should be tested in advance, and whether there is reimbursement for testing and/or treatment.

“And perhaps just as importantly, if people perceive there might be a definitive treatment for Alzheimer’s, why would they enroll in a clinical trial for another drug in development? I’m very concerned that this might put a damper on future investigations and clinical trials for other Alzheimer’s drugs in the pipeline,” Troen says.

“As geriatricians, we have a special opportunity and responsibility to address the entire gamut of medical, social and humanistic issues that arise when seeking to maintain and hopefully enhance the quality of life of dementia patients and their families. It is not compellingly clear to me at this time whether aducanumab should be included in the arsenal of therapeutic interventions,” he concludes.