January 5, 2023

expert reaction to correspondence piece of a patient with cerebral haemorrhages who was receiving lecanemab and treated with t-PA for stroke

A correspondence paper, published in the New England Journal of Medicine (NEJM), looks at the case of a patient receiving lecanemab and treated with t-PA who had multiple cerebral haemorrhages.

Prof Rob Howard, Professor of Old Age Psychiatry, UCL, said:

“We now know of at least two Alzheimer’s disease patients who have died after strokes linked to use of lecanemab – a new treatment that works by clearing amyloid from the brain. In both cases, patients were additionally taking drugs that “thinned” their blood and are used to either reduce the risk of stroke or limit neurological damage during a stroke.

“While such fatal strokes do seem to be very rare (almost two thousand patients were eligible for lecanemab treatment, either as part of a placebo-controlled trial or in a post-trial extension), abnormalities that have the MRI brain scan appearances of a mini-stroke are seen in more patients who received the drug than placebo. This has raised understandable concerns about the safety of treatment, particularly when lecanemab is made available outside of a clinical trial, where patients may be older, have more additional medical problems and receive less intensive safety monitoring.

“Ultimately, we should recognise that this is a new drug with powerful effects in the brain and, until we have more data from people with Alzheimer’s disease treated in routine clinical practice and for longer periods than the trials, it makes sense to be cautious about the potential for causing harm as well as modest treatment benefits in our patients. Individual doctors will make their own decisions about prescribing lecanemab to their patients, based on the efficacy data from the clinical trials and their perception of the risks associated with treatment. My own view would be that the benefits of the treatment appear to be too tiny to justify the risks and I wouldn’t recommend this for my own patients.”

Dr Liz Coulthard, Associate Professor in Dementia Neurology, University of Bristol, said:

“This set of papers describe an important and sad case where a patient had a large stroke while taking lecanemab. While bleeding in the brain after treatment for stroke is common, the type and extent of bleeding look worse here than might be expected. It may be that being on lecanemab for Alzheimer’s disease caused more bleeding in the brain than expected in response to clot-busting therapy for stroke.

“It is very important to know about side effects of lecanemab so that we can counsel patients to decide if the treatment is in their best interests.

“As we start to use these new drug treatments for Alzheimer’s, we need an international registry where longer term effects of the drug are noted. Clinical trials are only over a shorter time and real-world longer term data collection should guide use of all medications. We need balanced reporting of side effects and real-world benefits to help us understand the long-term impact of treatment.

“We are starting to see clues that certain groups of people with Alzheimer’s may be more prone to the serious side effects of lecanemab. As we learn more, we will be able to tailor therapy to individual patients.”

More information about stroke that might be relevant:

“For most patients, despite the risk of bleeding, clot busting treatment (TPA) is still beneficial overall, but there are some patients who cannot have clot busting treatment because, for example, they have had recent surgery. For those patients, mechanical clot removal (thrombectomy) can treat the stroke, but this is only available in major centres and it needs to be performed very quickly after stroke. It maybe that being on lecanemab affects the way we treat stroke in our patients with Alzheimer’s, and this is important to know.”

‘Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke’ by Nicholas J. Reish et al. was published in NEJM

DOI: 10.1056/NEJMc2215148

‘Response to: Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke’ by Marwan Sabbagh and Christopher H. van Dyck was published in NEJM

DOI: 10.1056/NEJMc2215907

Declared interests

Prof Rob Howard: “No conflicts.”

Dr Liz Coulthard: “I have delivered trials for Eisai and Biogen and have received grant funding from Biogen.”