Professor Robert Howard. I spend half my week working with older people with mental health disorders and dementia and my research aims to develop and evaluate better treatments for my patients. Through the conduct of independent clinical trials - from earliest proof of efficacy concept through to phase III - we can provide powerful evidence of what works and what doesn’t. Within the Department we have potential PhD supervisors with interests in dementia, depression, psychosis and anxiety disorders in older people. We’ve experts in epidemiology, PET and MR imaging, wet lab science and old fashioned clinical studies. Please come and talk to me if you think you might have an interesting idea but need to find someone to help you to develop it into your own supervised research project.
Abstract Almost a generation has passed since the cholinesterase inhibitors and memantine were licensed for the treatment of Alzheimer’s disease and, after what has felt like an endless series of treatment failures, the amyloid antibodies aducanumab and lecanemab have recently shown efficacy in phase 3 trials and received accelerated approval by the US FDA. We are standing on the threshold of a new era of treatments for neurodegenerative disorders and there is understandable excitement about the prospect of intervening to slow progression of disease.
Treatment with amyloid antibodies is invasive and not without risks of serious side-effects, including, rarely, death. The administration and safety monitoring of these drugs will require completely new clinical services and access to trained staff and imaging facilities that are not currently available within the NHS. The financial implications of this, even if the drug is provided for free, would be enormous.
Unfortunately, treatment benefits demonstrated within the phase 3 trials appear to be modest. In absolute terms, they are about 50% of what is generally considered to represent the minimum clinically important treatment difference and the trials were not designed to definitively demonstrate that the course of neurodegeneration had been modified.
There also appears to be little or no clear association between the amount of amyloid cleared from the brain and measured benefits in cognition and function, casting doubt on the role of amyloid as a driver of neurodegeneration. Despite such concerns, many have expressed enthusiasm for these treatments. An argument has been made that, in the presence of disease course modification, absolute differences between drug and placebo after 18 months of treatment do not fairly represent the full benefits of treatment. I will review the results of the amyloid antibody trials, the status of the evidence for disease course modification and the apparent clinical effectiveness of treatment with lecamemab.
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