New Alzheimer’s drugs aren’t worth the hype — and here’s why

One of my notable childhood memories is of my grandparents living with dementia and then dying from it. As with dementia, we were dealt a double whammy: watching my grandparents lose their identity, and seeing the suffering of those closest to them.

As a junior doctor on a specialist dementia ward when I was in my twenties, I watched the same stories play out in family after family, and felt largely powerless to help. Now, in my 30s, I conduct public health research to understand what we can do to prevent, delay or improve the experience of dementia – The leading cause of death in England.

Naturally, this leaves me desperate for good news about treatment options for Alzheimer’s disease – the leading cause of dementia. Enter three medications (aducanumab (trade name Adohelm), com. lecanemap (to my lips) and com. donanemab) that remove amyloid, the protein thought to cause Alzheimer’s disease. Unlike many of their predecessors, Which also succeeded in removing amyloid From the brain, these drugs were the first to slow cognitive decline.

This breakthrough has been hailed as ‘The beginning of the end for Alzheimer’s disease’But how useful are these medications? There are four main shortcomings to consider:

1. Small benefits: In the donanemab trial, people taking the drug dropped an average of ten points on a 144-point cognitive scale. The placebo group decreased by 13 points.

Consistent with the patterns in the trials for the other two drugs, this tells us that all the groups in all of these trials declined and that the amount of reduction that was avoided by taking the drug – in this case donanemab – (three points) was much less than the amount of reduction that still occurred (ten points ). The difference in the amount of decline was so small that it would occur It may not be noticeable For the doctors who care for these patients.

2. Side effects: Through regular magnetic resonance imaging (MRI) scans, one in six people taking licanimab had evidence of bleeding in the brain, and one in eight had brain swelling.

Sometimes, regular scans pick up these diseases in dementia patients. Indeed, one in 11 of the participants in the placebo group had evidence of bleeding, while one in 59 had swelling. For most people, these events would have been detectable only by MRI and not by the appearance of any specific symptoms. However, the effects of this drug’s damage to the brain, especially the long-term effects, are unknown.

Unfortunately, there was also A.J Few deaths attributed to these drugs.

3. Very expensive: Aducanumab was marketed in the US for US$45,000 (£35,000) per patient per year (later reduced to US$20,000 due to increased demand), and lecanemab for US$26,500. This is only for the drug itself. Health systems also need to pay for additional scans to test eligibility, monitor and manage side effects, and staff to run infusion clinics.

The donanemab trial suggested that treatment could be ended when brain scans show sufficient amyloid clearance. But we don’t know if the amyloid will come back after some time. Regular monitoring of amyloid recurrences and frequent bouts of treatment would add to the costs.

There are other obligations for patients: coming to the centers every two to four weeks for drug injections, regular monitoring, and worrying about side effects.

The patient's arm is prepared for the infusion.
Patients will need regular infusions.
Dragon Pictures/Shutterstock

4. Highly selective experiences: It is accepted that not all trial “efficacy” (the effect seen in the course of a specialized trial, designed to increase the likelihood of treatment success, eg including only uncomplicated cases) will translate into clinical “efficacy” (the effect seen when drugs are used). given to relatively more complex patients in busy real-world clinical settings). This is concerning, because there is little wiggle room before the effects become undetectable. Although this is the case for all diseases, Alzheimer’s disease is likely to be an extreme example.

Of every 10 patients doctors believed qualified for these trials, seven or eight were rejected. People with brain diseases other than amyloid, such as blood vessel damage or Lewy bodiesAnd those with other major medical problems, which might cloud the trial results and increase the risk of side effects, were excluded.

If drug eligibility is restricted to match trial eligibility, very few people will be eligible. If the eligibility is wider, the effects that are already small are likely to be smaller and the side effects more noticeable.

Deep deficiencies

there is more. The trials selected people in the early stages of the disease — when symptoms had only recently appeared — and successfully removed the amyloid, yet the patients’ amyloid levels continued to decline at about the same speed. So, researchers inevitably wonder: Maybe we need to start taking medications earlier? but how?

The people in the trials were, on average, five to 10 years younger than most people diagnosed with Alzheimer’s disease in the United States. we And United kingdom. Detecting the disease early is problematic because most people have amyloid but do not have cognitive symptoms They will not develop dementia before they die.

Unfortunately, I don’t think these medications can make much of a difference for people who currently or soon have Alzheimer’s disease. The shortcomings are so profound that, despite decades of expensive trials and patient sacrifices, I believe it is time to eliminate the amyloid blip and prioritize exploring other, neglectedOptions for treating dementia.

This is not the beginning of the end of Alzheimer’s disease, but perhaps it should be the end of the course of anti-amyloid medications.

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