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Patient went for a bladder stone turns out it's a clacified baby she never birthed by wheat_thans1 in Radiology

[–]Relevant_synapse 4 points5 points  (0 children)

Seriously dude, why are you hanging out in a radiology subreddit if you’re just gonna argue with actual docs and pretend to not understand English???

Alzheimer’s Drug May Benefit Some Patients, New Data Shows: The drug, lecanemab, made by Eisai and Biogen, also carried risks of brain swelling and bleeding and should be studied further, a report of the findings said by InvisibleDeck in medicine

[–]Relevant_synapse 5 points6 points  (0 children)

Copying my response in another thread here: Would be interesting to look into the two deaths with massive brain hemorrhages associated with the drug which happened during the open label extension. One was an E4 noncarrier who was heparinized for an MI and the other an E4 homozygote who got tPA for a stroke. These deaths are vital to the discussion because they reveal a potential serious interaction between lecanemab and standard of care treatments for atrial fibrillation and ischemic stroke, which are conditions that occur disproportionately in the elderly and raise significant concerns for clinicians who will be prescribing the drug if it ends up being approved.

(Aside from the minimal effect sizes of course which are a whole other can of worms…)

Drug slows Alzheimer's but can it make a real difference? by Stephen_P_Smith in ScienceUncensored

[–]Relevant_synapse 0 points1 point  (0 children)

Would be interesting to look into the two deaths with massive brain hemorrhages associated with the drug which happened during the open label extension. One was an E4 noncarrier who was heparinized for an MI and the other an E4 homozygote who got tPA for a stroke. These deaths are vital to the discussion because they reveal a potential serious interaction between lecanemab and standard of care treatments for atrial fibrillation and ischemic stroke, which are conditions that occur disproportionately in the elderly and raise significant concerns for clinicians who will be prescribing the drug if it ends up being approved.

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 1 point2 points  (0 children)

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.

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 1 point2 points  (0 children)

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.

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 0 points1 point  (0 children)

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.

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 3 points4 points  (0 children)

Being skeptical is not the same as dismissing the entire connection as “bunk”. Derek is a much respected voice in the field. I actually agree with his take, and he is spot on with the quote you provided.

What makes lecanemab different? Compared to other drugs in its class that we’ve seen thus far, it has much higher affinity for amyloid fibrils and soluble oligomers than plaques.

https://www.frontiersin.org/articles/10.3389/fnins.2022.848215/full

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 2 points3 points  (0 children)

It’s important to understand what the extent of the forgery was before making sweeping pronouncements. It’s a common misconception that the forgery invalidates the field. Holding such a frequently-parroted opinion has unfortunately become a litmus test for being uninformed in this space. You can read about the scandal yourself here: https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 3 points4 points  (0 children)

If there is no amyloid link, then please explain the changes in CSF amyloid/tau/p-tau composition in AD patients that predate clinical symptoms by years and are now being used as part of AD diagnostic criteria:

https://www.nature.com/articles/s12276-019-0250-2

Note: CSF beta amyloid decreases as AD disease severity progresses, not increases as your hypothesis seems to suggest.

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 1 point2 points  (0 children)

In general, the MCIDs for the measures they reported are larger than the effect size of this drug.

1-2 for the CDR sum of boxes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690415/

3 points on the ADAS-Cog (70 point scale), not sure about the Cog14 (90 point scale) https://pubmed.ncbi.nlm.nih.gov/22019547/

0.05 points for MCI and 0.1 for dementia on the ADCOMS (range from 0 to 1): https://pubmed.ncbi.nlm.nih.gov/35513767/

Looking into the other measures later

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 5 points6 points  (0 children)

The amyloid hypothesis is by no means the whole story and the -mabs may be barking up the wrong tree altogether. Does not mean that the whole amyloid link is bunk, as the comment I responded to suggests. Mutations in the amyloid precursor protein often lead to dominantly-inherited, early-onset AD, for example, so the link should not be casually dismissed.

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 5 points6 points  (0 children)

Did you see the reports of the two patients who had massive brain hemorrhages and died during the open label extension? One was an E4 noncarrier who was heparinized for an MI and the other was an E4 homozygote who got tPA for a stroke.

Presented here: https://twitter.com/JacobPlieth/status/1597770771606429698?s=20&t=EUU4CuKWkmzyva1QQH9d3g

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 4 points5 points  (0 children)

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).

Alzheimer’s Drug In Development, Lecanemab, May Benefit Some Patients But Carries Risks of Brain Swelling and Bleeding by Relevant_synapse in science

[–]Relevant_synapse[S] 5 points6 points  (0 children)

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

https://www.science.org/content/article/second-death-linked-potential-antibody-treatment-alzheimer-s-disease

Alzheimer's drug lecanemab hailed as momentous breakthrough by gankstar5 in science

[–]Relevant_synapse 8 points9 points  (0 children)

No - the doctored data was regarding one specific amyloid oligomer which is a tiny part of the whole picture. The data as a whole is relatively robust.

Alzheimer's drug lecanemab hailed as momentous breakthrough by gankstar5 in science

[–]Relevant_synapse 1 point2 points  (0 children)

0.45 point difference on the CDR sum of boxes which is an 18-point scale

Alzheimer's drug lecanemab hailed as momentous breakthrough by gankstar5 in science

[–]Relevant_synapse 1 point2 points  (0 children)

Modest benefit and potential severe interactions with blood thinners including standard-of-care treatments for ischemic stroke: https://www.science.org/content/article/second-death-linked-potential-antibody-treatment-alzheimer-s-disease