Relevant_synapse OP t1_iyba9fe wrote
TL:DR - Modest benefit and potential severe interactions with blood thinners including standard-of-care treatments for atrial fibrillation and ischemic stroke:
Primary endpoint: adjusted least-squares mean change on the Clinical Dementia Rating Sum of Boxes (an 18-point scale measuring cognitive function) from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001).
2 deaths associated with the drug in the open-label extension, both with massive brain hemorrhages: an 87 year old man previously on Eliquis who was heparinized for an acute myocardial infarction, and a 65 year old woman who received tPA for acute ischemic stroke.
https://amp.cnn.com/cnn/2022/10/28/health/alzheimers-drug-lecanemab-trial/index.html
Relevant_synapse OP t1_iybfnq4 wrote
Other select findings:
Greater reductions in brain amyloid burden with lecanemab than with placebo on PET (difference, −59.1 centiloids; 95% CI, −62.6 to −55.6) in a subset of 698 participants.
Adjusted mean change from baseline at 18 months in the 90-point ADAS-cog14 score (another measure of cognitive function) was 4.14 in the lecanemab group and 5.58 in the placebo group (difference, −1.44; 95% CI, −2.27 to −0.61; P<0.001).
The most common adverse events (affecting >10% of the participants) in the lecanemab group were infusion-related reactions (26.4% with lecanemab and 7.4% with placebo); amyloid-related imaging abnormalities (ARIA) with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H; 17.3% with lecanemab and 9.0% with placebo); ARIA-E (12.6% with lecanemab and 1.7% with placebo).
sockalicious t1_iyd0m0d wrote
From the Science artice you linked:
>Still, one reason to think lecanemab contributed to the woman’s death is that her autopsy revealed widespread cerebral amyloid angiopathy (CAA), a condition in which amyloid deposits gradually replace the smooth muscle of blood vessel walls. Castellani, Nicoll, and others who reviewed her case suspect CAA made her blood vessels vulnerable to weakening when lecanemab did what it is expected to do: strip amyloids from the brain. The tPA treatment then likely ruptured those weakened vessels, leading to serious ARIA—and apparently fatal brain bleeding, according to the Northwestern report authors and independent CAA or Alzheimer’s experts.
What the article doesn't mention is that CAA would be a contraindication to t-PA therapy for stroke, whether someone had received anti-amyloid therapy or not.
Considering t-PA therapy for stroke is always a "chaotic scene" because there is a brief window of time after stroke onset that it can be used, and the standard imaging studies used to see if t-PA is indicated don't detect CAA - you have to look back in the record and see if an MRI has been done, and that lookback isn't always possible in the emergency department setting.
Relevant_synapse OP t1_iyd1dof wrote
If you go back to the trial protocol, the participants’ MRIs had to have <4 microhemorrhages in order to be enrolled. Known CAA would have been a contraindication to even being in the trial. It’s reasonable to believe that there was no indication that this woman had CAA before she received tPA and all hell broke loose, but we obviously won’t know for sure until the case report is published.
sockalicious t1_iyd2z8h wrote
I have rarely seen such a dramatized account of a medical complication in a science journal, by the way. When folks die in cancer trials, is it commonplace to describe their screaming, or the visit of the priest to the bedside?
Relevant_synapse OP t1_iyd3hpx wrote
People don’t tend to die from massive brain bleeds in cancer trials. The priest visit depends on the patient’s religious beliefs, but is pretty commonplace in my experience as an ICU physician.
sockalicious t1_iyd3x66 wrote
I am a neurologist. People do indeed die screaming on the cancer ward, happens all the time. My point was just that it's a little odd to find these details in a science journal article about an investigational drug.
Relevant_synapse OP t1_iyd430n wrote
I am also a neurologist, but my patients tend to die intubated since I’m neurocrit. This piece hit close to home because it’s literally what I do, and unfortunately what you think may be a dramatic description I see in daily life.
[deleted] t1_iybdgwo wrote
[removed]
Viewing a single comment thread. View all comments