Drugs aimed at slowing Alzheimer’s disease progression “make no meaningful difference to patients” while raising the risk of brain swelling and bleeding, a new review has claimed.
However, charities have swiftly challenged these findings, accusing experts of unfairly combining failed and successful drug trials.
Researchers behind the review stated that the effects of these medicines on individuals with early-stage Alzheimer’s and dementia were “either absent or consistently small”.
Edo Richard, a professor of neurology at Radboud University Medical Centre in the Netherlands, noted his team observed “results from trials over the last two decades ‘are not consistent'”.
Charities argue that the review’s authors have attempted to “paint an entire class of drugs with the same brush”, potentially undermining the benefits of certain treatments. Anti-amyloid medicines work by binding to and clearing protein deposits in the brains of those with Alzheimer’s, a process intended to slow cognitive decline.
Two anti-amyloid drugs – lecanemab and donanemab – are licensed for use in the UK.
The treatments were not approved for use on the NHS after the National Institute for Health and Care Excellence (Nice) deemed their benefits “too small” to justify the cost.
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 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.”
Reacting to the findings, Dr Richard Oakley, associate director of research and innovation at the Alzheimer’s Society, said: “This review’s conclusions make the picture look bleaker than it really is, as authors combined results for a majority of failed drug trials with a small number of more recent successful trials.
“This includes the trials for lecanemab and donanemab which the UK medicines regulator agreed bring a modest but meaningful benefit for people with early-stage Alzheimer’s.
“It’s essential that we interpret this review with nuance and avoid taking a sledgehammer to decades of pioneering scientific study.”
Jonathan Schott, professor of neurology and group leader of the UK Dementia Research Institute at UCL, said: “By combining studies of different drugs, many of which have long since been disbanded, several of which had little or no effects on beta-amyloid, and most of which have failed in randomised clinical trials, it is almost inevitable that the conclusion will be that as a group they are clinically ineffective.”
Dr Susan Kohlhaas, executive director of research at Alzheimer’s Research UK, said the charity regularly heard from families impacted by dementia who said that even a delay of several months in their loved one’s decline “could provide valuable, meaningful time” that “shouldn’t be minimised”.
She said: “Crucially, this study is attempting to paint an entire class of drugs with the same brush even though we know different anti-amyloid treatments can act in different ways.
“Anti-amyloid treatments will not be the whole answer to curing Alzheimer’s, and research is already moving towards a wider range of biological targets.
“But it’s not accurate to dismiss their impact as ‘trivial’, especially when the analysis has clear constraints that limit what it can tell us.”
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.
Issues that would be revisited include the conclusion on the quality of life of those caring for Alzheimer’s patients, as well as evidence provided by NHS England estimating the cost of giving the treatments by infusion.
