Cochrane review finds Alzheimer's drugs ineffective and risky

A new Cochrane review has concluded that anti-amyloid drugs for Alzheimer's disease make no meaningful difference to patients and increase the risk of brain swelling and bleeding, casting doubt on the value of expensive treatments recently licensed in the UK.

The Cochrane review, which examined 17 studies involving 20,342 patients, found that anti-amyloid drugs for Alzheimer's disease do not provide a clinically meaningful benefit. According to the review, the drugs increase the risk of brain swelling and bleeding, raising serious safety concerns. Francesco Nonino, a neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna and lead author of the review, 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." He added that while early trials showed statistically significant results, these do not translate into clinical relevance for patients.

The drugs lecanemab and donanemab are licensed for use in the UK, but the National Institute for Health and Care Excellence (Nice) has ruled that their benefits are too small to warrant NHS funding. The treatments are expensive, with an 18-month course costing around £90,000 privately. This has left patients and families in a difficult position, as the drugs are available but not covered by the health service. Edo Richard, professor of neurology at Radboud University Medical Centre, said: "I would tell them, I think you will probably not benefit from these drugs and they're burdensome for you and your family. I think it's extremely important that we're honest to our patients about what they can expect, I'm always wary to avoid giving people false hope."

However, some charities and experts have disputed the Cochrane review's methodology. They argue that combining failed older drug trials with successful newer ones is flawed. Professor Robert Howard at University College London called the review "fundamentally flawed" and said it blurs the evidence. He stated: "It was unfortunate and unfair to families affected by dementia that these drugs have been hyped in a way that is not supported by robust science and that will have raised false hopes." Professor Bart De Strooper, also at UCL, said: "The flaw in this review is fundamental." These experts maintain that the newer drugs do slow cognitive decline meaningfully, contrary to the review's conclusions.

The Cochrane review acknowledges that the drugs slow cognitive decline but not enough to make a meaningful difference to patients. This distinction between statistical significance and clinical relevance is at the heart of the debate. The review's authors argue that the effect size is too small to be noticeable by patients or clinicians. Nonino explained: "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 disagreement over what constitutes a meaningful benefit has implications for whether patients and healthcare systems should consider these expensive drugs as viable treatment options. Unknowns remain about the specific criteria used to define 'meaningful difference', the comparative frequency and severity of side effects between different drugs, and the exact cost-effectiveness threshold used by Nice. Ongoing trials and real-world studies may eventually clarify the long-term benefits, but for now, the evidence remains contested.