Some Alzheimer's drugs make 'no meaningful difference'

Drugs that are said to slow the progression of Alzheimer's disease "make no meaningful difference to patients" while increasing the risk of swelling and bleeding in the brain, according to a new review.

The effects of the medicines on those with early-stage Alzheimer's and dementia were "either absent or consistently small", researchers said.

But charities have challenged the findings and said experts have attempted to "paint an entire class of drugs with the same brush" by combining failed drug trials with more recent successful trials.

Anti-amyloid medicines bind to the protein which builds up in the brains of people living with Alzheimer's, clearing deposits and slowing down cognitive decline.

But Edo Richard, professor of neurology at Radboud University Medical Centre in the Netherlands, said his team noticed that results from trials over the last two decades "are not consistent".

The new Cochrane review looked at 17 studies involving 20,342 patients overall.

Most had either mild cognitive impairment (MCI), which causes problems with thinking and memory, dementia, or both, with a mean age of 70 to 74.

The studies included trials on anti-amyloid drugs lecanemab and donanemab, as well as aducanumab, which has been discontinued by its manufacturer, and bapineuzumab, crenezumab and solanezumab, which were discontinued after failed trials.

The analysis found that the effects of these drugs on cognitive function and dementia severity after 18 months was "trivial".

According to Prof Richard, the differences made by the treatments were "far below the minimal effect that's needed to be noticeable at all for patients and caregivers".

Francesco Nonino, neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna in Italy, said: "Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients.

"There is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect.

"While early trials showed results that were statistically significant, it is important to distinguish between this and clinical relevance.

It is common for trials to find statistically significant results that do not translate into a meaningful clinical difference for patients."
The drugs could also increase the risk of swelling and bleeding in the brain, according to the study.

These side effects were seen in brain scans and caused no symptoms for most patients, although the long-term impact was unclear.

Mr Nonino also highlighted that most studies reported after 18 months, which he described as a "relatively short" window "in the context of a slowly progressive condition like Alzheimer's".

"Also it has to be remembered that these drugs in clinical practice may likely be used for much more than 18 months," he said.

Prof Richard, who runs a dementia clinic, said he was honest with patients about the effect of the approved drugs and that they were "too small for patients and caregivers to notice".

He said he also highlighted potential side effects, the need for various scans and tests to confirm eligibility, and that patients would need to visit the clinic every two to four weeks to have the treatment from an IV drip.

He added: "I would tell them...

I think you will probably not benefit from these drugs, and they're burdensome for you and your family.

"I just think it's extremely important that we're honest to our patients about what they can expect...

there's nothing more that I would like as a doctor to finally be able to prescribe them a drug that provides a bit more hope to the patients and their families, but I'm always wary to avoid giving people false hope."
The review comes after it emerged Nice is looking again at evidence on donanemab and lecanemab following successful appeals by their manufacturers Eli Lilly and Eisai.