New FDA-approved drug, Aduhelm,for Alzheimer's

[neglect]

Btw this was shared on Twitter by Alberto Espay, chair at Cincy. Well respected neurologist, author of many books in neuro/cognitive world.
View attachment 387967

He's not respected anymore. Really pathetic stuff below, but nothing new given the false statements above.

The TLDR version is that he ignored the FAERS warnings and limitations, tried to publish the reported bad events with the anti-amyloid drugs, got denied, then did a pre-print without noting the severe limitations, which got picked up by the NY Times among others, and now his coauthors forced him to retract it (retracting a pre-print!). Too late, and he put a stain on the co-authors.

https://www.science.org/content/article/preprint-alzheimer-s-drug-deaths-ignites-dispute-among-authors

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Members don't see this ad.

 

[neglect]

Btw this was shared on Twitter by Alberto Espay, chair at Cincy. Well respected neurologist, author of many books in neuro/cognitive world.

It is getting worse for Espay.

Science has now included a disclaimer that the preprint was withdrawn, but its article still has a sticking point for UC: The article suggests that UC does not offer lecanemab treatment and claims that to Espay's knowledge, "not a single patient has gotten the monoclonal antibody lecanemab" there.

However, Alzheimer's patients have been receiving lecanemab at UC for over a year.

"We initiated lecanemab treatments in October 2023 and currently have 53 patients undergoing treatment, and six eligible but waiting for insurance approval," Rhonna Shatz, DO, medical director of the UC Memory Disorders Centeropens in a new tab or window, told MedPage Today. Three patients who received lecanemab had asymptomatic amyloid-related imaging abnormalities (ARIA), including two who discontinued treatment. None died.

So he also lied about his institution not giving lecanemab. Obviously that's on the reporter as well.

Alzheimer's Data Withdrawn

Researchers do not stand by claims made about lecanemab deaths

www.medpagetoday.com

 

[neglect]

Btw this was shared on Twitter by Alberto Espay, chair at Cincy. Well respected neurologist, author of many books in neuro/cognitive world.

His lies resulted in a correction in the (still bad) NY Times article. The correction itself has problems, but whatever, the journalists aren't experts.

A few things for others, since you're not going to respond. Don't get me wrong, I respect this - best to stay down.

This is a great lesson for anyone. Never approach empirical questions (is this drug dangerous, does it work? Is my partner hooking up and using drugs?) without engaging with evidence. Espay never engaged with evidence. Even after all this he was STILL saying that he just "knows" these drugs are dangerous and he is going to go find evidence for this. That's nonsense, but far more damaging is that the lesson was lost on him.

Have a theory, good! Want the theory to be true, great! Then try to tear it down. Find evidence that falsifies it. It evidence doesn't falsify the theory, it stands. That's science.

Espay is more like other frauds and tricksters like RFK, American Frontline Doctors, and Mehmet Oz. He just knows. Or pretends to know. Then he goes out and says something random proves he's right (the repeating reports in the FAERS dataset, never mind the RCT data). This is a dangerous thought pattern.

He was playing with fire. Over the past few years he's become something of a media gadfly for the negative take on the new AD drugs. We even see him here. Patients get influenced by media coverage of science. His lies did real damage. And now he's been exposed. There can be no doubt other journalists will take note.

So that's the biggest lesson. That lies usually come home, which we will continue to see play out.

 

[deathmerchant]

His lies resulted in a correction in the (still bad) NY Times article. The correction itself has problems, but whatever, the journalists aren't experts.

A few things for others, since you're not going to respond. Don't get me wrong, I respect this - best to stay down.

This is a great lesson for anyone. Never approach empirical questions (is this drug dangerous, does it work? Is my partner hooking up and using drugs?) without engaging with evidence. Espay never engaged with evidence. Even after all this he was STILL saying that he just "knows" these drugs are dangerous and he is going to go find evidence for this. That's nonsense, but far more damaging is that the lesson was lost on him.

Have a theory, good! Want the theory to be true, great! Then try to tear it down. Find evidence that falsifies it. It evidence doesn't falsify the theory, it stands. That's science.

Espay is more like other frauds and tricksters like RFK, American Frontline Doctors, and Mehmet Oz. He just knows. Or pretends to know. Then he goes out and says something random proves he's right (the repeating reports in the FAERS dataset, never mind the RCT data). This is a dangerous thought pattern.

He was playing with fire. Over the past few years he's become something of a media gadfly for the negative take on the new AD drugs. We even see him here. Patients get influenced by media coverage of science. His lies did real damage. And now he's been exposed. There can be no doubt other journalists will take note.

So that's the biggest lesson. That lies usually come home, which we will continue to see play out.



View attachment 395298

I agree with you about what Espay did, specifically in these situations is wrong. None of that changes anything about what I, or other neurologists in many countries, can see and interpret what the data shows.

 

[neglect]

I agree with you about what Espay did, specifically in these situations is wrong. None of that changes anything about what I, or other neurologists in many countries, can see and interpret what the data shows.

And what, exactly, did he do? You missed his fundamental flaw, I suspect, because you share it.

So I'll tell you. He ignored the data and came to an opinion that was unburdened by empiricism, just like the rest of his now disgraced "coauthors." The rest followed naturally from wrong premises. FAFO. It would even be funny if he hadn't harmed patients.

 

[deathmerchant]

And what, exactly, did he do? You missed his fundamental flaw, I suspect, because you share it.

So I'll tell you. He ignored the data and came to an opinion that was unburdened by empiricism, just like the rest of his now disgraced "coauthors." The rest followed naturally from wrong premises. FAFO. It would even be funny if he hadn't harmed patients.

My understanding is he overcalculated the amount of deaths from these drugs. Again, that doesn't change anything about the effectiveness of these drugs- for short term miniscule at best and long term (>10 years) potentially detrimental.
And the fact that the risk of serious complications is still very high.
And the cost burden plus healthcare system burden- invasive testing/MRIs/frequent visits is extremely high.
And many neurologists have looked at the data and said "Meh'
And amyloid hypothesis is still on shaky foundations.

Also these studies haven't even factored this fact that - one of the highest causes of mortality and morbidity is CVA and ACS in this population and these patients won't be good candidates for thrombolysis and potentially very high risk for anticoagulation in case they had an acute coronary syndrome or PE. Your dud drug will kill them and bankrupt them in many ways.

I've said this before- Rivastigmine had better results than these drugs without any serious side effects. And why do you think patients are getting severe brain edema and brain hemorrhages from this medication?- Upto 40% in certain subsets and if these many patients are getting clinically significant complications, how many do you think are getting subclinical damage which will accumulate over the years?

 

[neglect]

My understanding is he overcalculated the amount of deaths from these drugs. Again, that doesn't change anything about the effectiveness of these drugs- for short term miniscule at best and long term (>10 years) potentially detrimental.
And the fact that the risk of serious complications is still very high.
And the cost burden plus healthcare system burden- invasive testing/MRIs/frequent visits is extremely high.
And many neurologists have looked at the data and said "Meh'
And amyloid hypothesis is still on shaky foundations.

Also these studies haven't even factored this fact that - one of the highest causes of mortality and morbidity is CVA and ACS in this population and these patients won't be good candidates for thrombolysis and potentially very high risk for anticoagulation in case they had an acute coronary syndrome or PE. Your dud drug will kill them and bankrupt them in many ways.

I've said this before- Rivastigmine had better results than these drugs without any serious side effects. And why do you think patients are getting severe brain edema and brain hemorrhages from this medication?- Upto 40% in certain subsets and if these many patients are getting clinically significant complications, how many do you think are getting subclinical damage which will accumulate over the years?

ME:
"The data shows no significant difference between those who got ARIA and those who didn't. So your suspicion is unfounded, although subgroup analysis is a weak and limited look at the data.

Your belief that acetylcholinesterase inhibitors "slowed decline" is false. These medications increase acetylcholine. There is no mechanism by which they can slow decline. The fact you would write this means you shouldn't write anything else on the matter.

But it gets worse, because you say the data validates the idea that "there is no direct correlation with amyloid and dementia." I'm hard pressed to think of a less intelligent thought. I suspect you got this meme from other cynics who look at differences within the treatment group, but ignore the actual trial results.

In brief, donanemab gets rid of amyloid (it targets fibular amyloid). It met primary, secondary, and biomarker outcomes, including lowering soluble tau. So the conclusion from those who have much more expertise than you: getting rid of amyloid slows the disease."

 

[deathmerchant]

ME:
"The data shows no significant difference between those who got ARIA and those who didn't. So your suspicion is unfounded, although subgroup analysis is a weak and limited look at the data.

Your belief that acetylcholinesterase inhibitors "slowed decline" is false. These medications increase acetylcholine. There is no mechanism by which they can slow decline. The fact you would write this means you shouldn't write anything else on the matter.

But it gets worse, because you say the data validates the idea that "there is no direct correlation with amyloid and dementia." I'm hard pressed to think of a less intelligent thought. I suspect you got this meme from other cynics who look at differences within the treatment group, but ignore the actual trial results.

In brief, donanemab gets rid of amyloid (it targets fibular amyloid). It met primary, secondary, and biomarker outcomes, including lowering soluble tau. So the conclusion from those who have much more expertise than you: getting rid of amyloid slows the disease."

It’s clear to me you have tunnel vision and various biases, I’m guessing because you have spent a lot of your time and energy over this and now it’s being appropriately questioned. It’s also clear that you are incapable of making the complex clinical decisions required of a good physician that factor multiple things, some of which I pointed out in my above post. Esp the most basic principle of medicine - ‘do no harm’.
Finally, I don’t know why I keep taking the bait and replying to you when I know it’s going to start the same cycle 🤦🏻‍♂️. Someone tap me out please

 

[s5260205]

On a separate note for those who do prescribe anti-amyloid monoclonal antibodies, has anyone started using Kisunla, and any reason for prescribing one over the other?

 

[neglect]

On a separate note for those who do prescribe anti-amyloid monoclonal antibodies, has anyone started using Kisunla, and any reason for prescribing one over the other?

Yes. First of all, thank you for taking care of your patients and attending to their long term wellbeing. As you see, there is a lot of medical misinformation, nearing delusions, about these drugs.

Donanemab; easier burden as less treatments and limited to 1.5 years, but probably more aria. We are treating between 5-10. I’m also about to take over a case from an academic center because they don’t offer the new titration, which is weird. I also helped with their trials. Ask me anything.

 

[Mickquik1]

But what does Sylvain E. Lesné have to say about this?

 

[neglect]

But what does Sylvain E. Lesné have to say about this?

His paper that claimed to find a type of amyloid oligomer was accused of scientific fraud, but has nothing to do with the approved medications.

What's your point?

 

[neglect]

Wash U has been busy. They have 234 patients treated with lecanemab, whom they studied extensively, published safety and baseline data today in JAMA Neurology.

Symptomatic amyloid-related imaging abnormalities (ARIA) are rare at 1-2% and all ARIA is less likely at 22% than in the phase 3 trial. There was a potential fear that people would use these drugs like drunken sailors. But Wash U did not limit the drug based on APOE or MRIs.

They will follow this cohort over time. Models suggest that small changes in a long disease progression may prolong independence by a year.

We are past the tipping point here. This retrospective observational study shows the drug is safe when given to appropriate patients. Many of the comments here were initially negative, and I hope the anonymous nature of this forum provides cover for quiet reflection and revision. To do that, knowing why one was wrong is useful. Some people are just lazy and nihilistic, others got polarized by adu and this was an anchoring bias.

 

[deathmerchant]

Ok I briefly looked at the study, nothing impressive really. Its easy to trick stats for 6 months esp when it comes to a long, slowly progressive disease with a lot of variability.


1. Most patients selected here were very functional MCI or very early Dementia and they still had a decline of CDR SB from 2.6 - 7.0 in 6 months!! which is not much different than untreated early MCI and worse than Cholinergics esp Rivastigmine in various studies. Honestly most of my patients do much better than that with lifestyle modification.
For eg: A 52-week, open-label, observational study evaluating tolerability, efficacy and physicians satisfaction of rivastigmine oral solution in Alzheimer's disease in Taiwan - Chuo-Yu Lee, Wen-Fu Wang, Jung-Lung Hsu, Yuan-Han Yang, Kai-Ming Jhang, 2025 ( Only 2 point drop in CDR SB in 1 year with Rivast)

"155 patients had a baseline CDR-SB an average of 2.6 (SD, 1.8) months before treatment initiation and a follow-up CDR-SB an average of 7.0 (SD, 2.9) months following lecanemab initiation."

2. For the subset of patients with mild dementia - 27% developed symptomatic ARIA. That's super high for me. considering minimal efficacy and costs. So as soon as patients reach mild dementia stage, the ARIA risk goes dramatically high and so it follows will keep getting worse as the disease progresses.
"patients with mild dementia (CDR of 1) at baseline had a 15-fold higher rate of symptomatic ARIA compared with patients with MCI or very mild dementia (CDR of 0.5) at baseline (27% vs 1.8%)."

3. Finally this study is looking at 4 doses over just 6 months. We know for sure this medication causes some degree of CNS damage (ARIA)- either symptomatic or asymptomatic. It follows that long term use will accumulate that damage. One of our main concern has always been how much long term detriment this will cause. Maybe if they look at these same patients 2-5 years down the line, we can make more informed decisions.

"In contrast, isolated ARIA-H slowly accrued over time (2% by 2 months and 5% by 4 months). Only 33 patients had follow-up longer than 10 months; the proportion of patients with an ARIA finding at 12 months of treatment was 29%"

Will probably have more critiques when I look at it in detail. Again I'm not against advances in neurology and dementia which we need.
I'm against pharma money grab and biased research practices at the expense of patients, esp when public trust in medicine/Doctors is at all time low.

 

[neglect]

Ok I briefly looked at the study, nothing impressive really. Its easy to trick stats for 6 months esp when it comes to a long, slowly progressive disease with a lot of variability.


1. Most patients selected here were very functional MCI or very early Dementia and they still had a decline of CDR SB from 2.6 - 7.0 in 6 months!! which is not much different than untreated early MCI and worse than Cholinergics esp Rivastigmine in various studies. Honestly most of my patients do much better than that with lifestyle modification.
For eg: A 52-week, open-label, observational study evaluating tolerability, efficacy and physicians satisfaction of rivastigmine oral solution in Alzheimer's disease in Taiwan - Chuo-Yu Lee, Wen-Fu Wang, Jung-Lung Hsu, Yuan-Han Yang, Kai-Ming Jhang, 2025 ( Only 2 point drop in CDR SB in 1 year with Rivast)

"155 patients had a baseline CDR-SB an average of 2.6 (SD, 1.8) months before treatment initiation and a follow-up CDR-SB an average of 7.0 (SD, 2.9) months following lecanemab initiation."

2. For the subset of patients with mild dementia - 27% developed symptomatic ARIA. That's super high for me. considering minimal efficacy and costs. So as soon as patients reach mild dementia stage, the ARIA risk goes dramatically high and so it follows will keep getting worse as the disease progresses.
"patients with mild dementia (CDR of 1) at baseline had a 15-fold higher rate of symptomatic ARIA compared with patients with MCI or very mild dementia (CDR of 0.5) at baseline (27% vs 1.8%)."

3. Finally this study is looking at 4 doses over just 6 months. We know for sure this medication causes some degree of CNS damage (ARIA)- either symptomatic or asymptomatic. It follows that long term use will accumulate that damage. One of our main concern has always been how much long term detriment this will cause. Maybe if they look at these same patients 2-5 years down the line, we can make more informed decisions.

"In contrast, isolated ARIA-H slowly accrued over time (2% by 2 months and 5% by 4 months). Only 33 patients had follow-up longer than 10 months; the proportion of patients with an ARIA finding at 12 months of treatment was 29%"

Will probably have more critiques when I look at it in detail. Again I'm not against advances in neurology and dementia which we need.
I'm against pharma money grab and biased research practices at the expense of patients, esp when public trust in medicine/Doctors is at all time low.

You're like RFK Jr. You use words and don't understand what they mean. This an open label retrospective study. There is no comparison groups. Your use of unmatched historical controls is exactly the type of statistically illiterate, fallacious thinking that makes you unable to see the phase 3 data clearly.

The baseline CDR was "months before treatment initiation." Think about that for a second. So your biases made you miss the fact that "The estimated rate of change over the treatment period was 1.11 CDR-SB per year."

But wait a second. You said that there was only a "2 point drop in CDR SB with rivastigmine." So by your very own unmatched historical control group showed almost DOUBLE the decline. That's you. Hilarious self own, so good that I made a meme to help you to understand your error:

It was 27% (8/30) who had the symptomatic ARIA within the higher CDR SUBGROUP. The total group had 5.7% with symptomatic ARIA whole group, 1.0% (2 total) had severe symptoms. Do you know what the multiplicity problem is? By your illogic, we can then assume that the 3 cases of symptomatic ARIA out of of 164 (1.8%) is true in the milder group, right? Serious question. Because it follows from what you said: "For the subset of patients with mild dementia - 27% developed symptomatic ARIA. That's super high for me." So MCI has super LOW ARIA. Right?

I'm not really speaking to you, since you're lost to your thought processes. You've clearly made public statements against the drug class and you have to dig in, poke holes in data generated by people who, unlike you, are capable, expert, and diligent enough to do this work. So, to other people out there: Wash U showed the drug can be given safely. So far the data is in line with the trials. People who cannot understand stats cherry pick the 'bad' ones, fail to understand the totality. Don't be like them.

 

[Spinothalamic]

I am sure that there will soon be more posts that are well thought out but will slowly devolve to snarky comments (actually I was typing this post when the post immediately above was posted--perfect timing!), but I guess I will make a couple of comments that MAY be able to be somewhat of a compromise.

1) Could we agree that the current data clearly shows an aggregate clinical benefit in patients who receive lecanemab, which works in a biologically plausible manner clearly distinct from something like a symptomatic medication such as donepezil, but there are differing opinions regarding whether the DEGREE of clinical benefit is "worth it" when considering societal/individual cost, risks, serial neuroimaging, etc?

2) Could we also agree that we are past the "tipping point", but far from what most people would consider a "good" treatment for a disease?

3) And finally, could we agree that (obviously) the answers will be much clearer when we have 10-year follow-up data as we are too early to definitively state long-term benefit/risk/cost-effectiveness?

Yes, I am partly trying to be a peacemaker but also I am interested in opinions from various neurologists. I am part of a larger private neurology group and we hardly use these medications.

 

[deathmerchant]

I am sure that there will soon be more posts that are well thought out but will slowly devolve to snarky comments (actually I was typing this post when the post immediately above was posted--perfect timing!), but I guess I will make a couple of comments that MAY be able to be somewhat of a compromise.

1) Could we agree that the current data clearly shows an aggregate clinical benefit in patients who receive lecanemab, which works in a biologically plausible manner clearly distinct from something like a symptomatic medication such as donepezil, but there are differing opinions regarding whether the DEGREE of clinical benefit is "worth it" when considering societal/individual cost, risks, serial neuroimaging, etc?

2) Could we also agree that we are past the "tipping point", but far from what most people would consider a "good" treatment for a disease?

3) And finally, could we agree that (obviously) the answers will be much clearer when we have 10-year follow-up data as we are too early to definitively state long-term benefit/risk/cost-effectiveness?

Yes, I am partly trying to be a peacemaker but also I am interested in opinions from various neurologists. I am part of a larger private neurology group and we hardly use these medications.

Honestly this is where I am at. Maybe one degree more pessimistic than this. But I am open to changing my mind in future.

 

[deathmerchant]

You're like RFK Jr. You use words and don't understand what they mean. This an open label retrospective study. There is no comparison groups. Your use of unmatched historical controls is exactly the type of statistically illiterate, fallacious thinking that makes you unable to see the phase 3 data clearly.

The baseline CDR was "months before treatment initiation." Think about that for a second. So your biases made you miss the fact that "The estimated rate of change over the treatment period was 1.11 CDR-SB per year."

But wait a second. You said that there was only a "2 point drop in CDR SB with rivastigmine." So by your very own unmatched historical control group showed almost DOUBLE the decline. That's you. Hilarious self own, so good that I made a meme to help you to understand your error:

View attachment 403667

It was 27% (8/30) who had the symptomatic ARIA within the higher CDR SUBGROUP. The total group had 5.7% with symptomatic ARIA whole group, 1.0% (2 total) had severe symptoms. Do you know what the multiplicity problem is? By your illogic, we can then assume that the 3 cases of symptomatic ARIA out of of 164 (1.8%) is true in the milder group, right? Serious question. Because it follows from what you said: "For the subset of patients with mild dementia - 27% developed symptomatic ARIA. That's super high for me." So MCI has super LOW ARIA. Right?

I'm not really speaking to you, since you're lost to your thought processes. You've clearly made public statements against the drug class and you have to dig in, poke holes in data generated by people who, unlike you, are capable, expert, and diligent enough to do this work. So, to other people out there: Wash U showed the drug can be given safely. So far the data is in line with the trials. People who cannot understand stats cherry pick the 'bad' ones, fail to understand the totality. Don't be like them.

The baseline CDR was "months before treatment initiation." Think about that for a second. So your biases made you miss the fact that "The estimated rate of change over the treatment period was 1.11 CDR-SB per year."

I get that, but you missed my main point, it is easy to get favorable numbers when you look at a tiny snapshot of a long disease. They never even followed any patient for more than 10 months. We all know why! And despite that just barely better than something that is basically a dud.

I would love for them to follow up after 2-3 years and maybe you can update us. I will be ready to change my mind! I treat hundreds of dementia patients, and like all neurologists, will be happy to have some good treatment options to offer to them.

Yes I agree MCI has super low ARIA. If you give it to normal people they will have even less ARIA! Just like if you give TNK to normal people without strokes they have less bleeding.

Again I am still open to changing my views, I need better long term efficacy and safety data before I subject one of my early dementia or MCI patients (who might have a decades to live) to ARIA, potential death, give false hope, make them have extensive testing and take away all their retirement savings!

 

[neglect]

I am sure that there will soon be more posts that are well thought out but will slowly devolve to snarky comments (actually I was typing this post when the post immediately above was posted--perfect timing!), but I guess I will make a couple of comments that MAY be able to be somewhat of a compromise.

1) Could we agree that the current data clearly shows an aggregate clinical benefit in patients who receive lecanemab, which works in a biologically plausible manner clearly distinct from something like a symptomatic medication such as donepezil, but there are differing opinions regarding whether the DEGREE of clinical benefit is "worth it" when considering societal/individual cost, risks, serial neuroimaging, etc?

2) Could we also agree that we are past the "tipping point", but far from what most people would consider a "good" treatment for a disease?

3) And finally, could we agree that (obviously) the answers will be much clearer when we have 10-year follow-up data as we are too early to definitively state long-term benefit/risk/cost-effectiveness?

Yes, I am partly trying to be a peacemaker but also I am interested in opinions from various neurologists. I am part of a larger private neurology group and we hardly use these medications.

When confronted with abject medical misinformation, snark is probably my best defense. Scientifically illiterate people torturing the data via post-hoc sub-studies to arrive at their lazy pre-specified bias should be called out. It is a type of diseased thinking that best weeded out in college at the latest!

Is that better?

1. Right, people differ about the degree of amyloid removal. The opinions that minimize change over time TEND fail to respect patient autonomy (and also do insurance company's bidding).

2. This is the same point as #2. But I'll use a different take on the response. When has perfection stopped medicine? The history of medicine contains huge wins: penicillin, Gleevac, vaccines, insulin and vat-grown insulin. These are amazing. Add some others: L-dopa, OCP, thorazine, ocrelizumab in RRMS. Totally life changing, sometimes life saving. But these are also very rare. Every drug that goes through development hopes to be a Gleevac. Then the data comes out and you get a Rilutek. Or copaxone/interferone. Or tPA. Or AZT. The list goes on and on.

ALS kills everyone, Rilutek or no, Radicava or no. NNT with tPA is 9 for major improvement and 3 for minor. Does that make treatment with these futile? Are they "good" enough? Is the patient or the disease worthy of the "cost, risks" and monitoring? Or do we just give up on them? Why should tPA get a pass? Because it is old?

What happened in these cases is that we keep innovating and iterating. Before you know it, we have polytherapy, things like HAART.

3. No, I do not agree things will be clear in 10 years because the data is clear now. We do not need to wait. There will never be better RCT data for lecanemab or donanemab in the disease than there is now: both have robust phase 2 and 3 trials showing the same thing: slowing of disease. What will become more clear with the next wave of anti-amyloid drugs is that amyloid removal slows down the disease, giving rise to a year of independence or so. At least one of the prevention trials will be positive. So what? Did you need 10 year outcomes to use ocrelizumab in PPMS? If not, why not?

Neurologists who fail to treat this fatal disease are the same as the ER docs who refuse to use thrombolytics.

 

[deathmerchant]

Sure bud. You are the best neurologist out there who cares for his patients more than everyone else and clearly understands research methodologies and pitfalls better than most of us, who should have been weeded out in college.

 

[Spinothalamic]

When confronted with abject medical misinformation, snark is probably my best defense. Scientifically illiterate people torturing the data via post-hoc sub-studies to arrive at their lazy pre-specified bias should be called out. It is a type of diseased thinking that best weeded out in college at the latest!

Is that better?

1. Right, people differ about the degree of amyloid removal. The opinions that minimize change over time TEND fail to respect patient autonomy (and also do insurance company's bidding).

I understand your point and agree in general. I suppose that both opinions that overestimate or underestimate clinical benefit can affect patient autonomy by giving them incorrect information with which to make decisions.

2. This is the same point as #2. But I'll use a different take on the response. When has perfection stopped medicine? The history of medicine contains huge wins: penicillin, Gleevac, vaccines, insulin and vat-grown insulin. These are amazing. Add some others: L-dopa, OCP, thorazine, ocrelizumab in RRMS. Totally life changing, sometimes life saving. But these are also very rare. Every drug that goes through development hopes to be a Gleevac. Then the data comes out and you get a Rilutek. Or copaxone/interferone. Or tPA. Or AZT. The list goes on and on.

ALS kills everyone, Rilutek or no, Radicava or no. NNT with tPA is 9 for major improvement and 3 for minor. Does that make treatment with these futile? Are they "good" enough? Is the patient or the disease worthy of the "cost, risks" and monitoring? Or do we just give up on them? Why should tPA get a pass? Because it is old?

What happened in these cases is that we keep innovating and iterating. Before you know it, we have polytherapy, things like HAART.

Also agree with this point. Hopefully these drugs pave the way for much more effective drugs! As above, patients should be given all of the information they need to make a decision regarding these drugs.

3. No, I do not agree things will be clear in 10 years because the data is clear now. We do not need to wait. There will never be better RCT data for lecanemab or donanemab in the disease than there is now: both have robust phase 2 and 3 trials showing the same thing: slowing of disease. What will become more clear with the next wave of anti-amyloid drugs is that amyloid removal slows down the disease, giving rise to a year of independence or so. At least one of the prevention trials will be positive. So what? Did you need 10 year outcomes to use ocrelizumab in PPMS? If not, why not?

This may show my ignorance, but I have actually really been hoping that the patients treated with the drug will have somewhat of a durable response which over time will cause an increasing separation between treatment and placebo arms. Do you not think this is possible or are you assuming this to be true? This is why I want longer term data. It is interesting to compare lecanamab to ocrelizumab in PPMS and I see what you are getting at.

Neurologists who fail to treat this fatal disease are the same as the ER docs who refuse to use thrombolytics.

You lost me here. Perhaps you mean that neurologists who refuse to prescribe this medication despite patients desiring it while truly understanding the benefit to cost/risks ratio (cost including financial, time spent with monitoring/infusions, and potential anxiety from pt/family about ICH) fit this analogy.

I have discussed this drug seriously with perhaps 50 patients/families (perhaps 50 really good potential candidates I mean) and none of them ultimately decided to proceed. You probably have a selection bias for more highly motivated patients who want the drug more so I understand a differential in drug utilization. I am community general neurology and also neuro-op. I do genuinely wonder if you think that my lack of patients on the drug means that I am not correctly explaining the pros and cons? I won’t take it personally

 

[neglect]

I understand your point and agree in general. I suppose that both opinions that overestimate or underestimate clinical benefit can affect patient autonomy by giving them incorrect information with which to make decisions.

There are no opinions that overestimate the clinical benefit. Those treating the disease have usually helped do the trials, respect the data because we see what went into it. No doctor is telling patients these meds will stabilize their disease, just slow it down.

But there are bad faith opinions that disrespect the data, as we see from @deathmerchant. A good faith opinion could include being circumspect with the degree of the slowing. Legitimate points about the trial duration, unblinding, absolute differences in the groups, expense, and medical utilization can be made and discuss. But you can't debate with bad faith partners who just make up nonsense and fallacies (medically illiterate substudies, post hoc analyses, and historical placebo group comparisons). The worst bad faith providers, not even sure if they are docs, don't diagnose and treat early AD (like geriatrics, and as an aside, if they stay alive as a field, they will embrace this). Like Espay, they aren't in the field; they focus on other things like health care policy; or are n-psych and can't prescribe anyway. Because they mostly can't and don't even diagnose early AD, there's no fear of loss of patient autonomy.

Also agree with this point. Hopefully these drugs pave the way for much more effective drugs! As above, patients should be given all of the information they need to make a decision regarding these drugs.

Reisa Sperling discussed these drugs as a "solid double." Again, no one is pretending this is a home run. This is not a Gleevac, HAART. But it is what we have right now.

This may show my ignorance, but I have actually really been hoping that the patients treated with the drug will have somewhat of a durable response which over time will cause an increasing separation between treatment and placebo arms. Do you not think this is possible or are you assuming this to be true? This is why I want longer term data. It is interesting to compare lecanamab to ocrelizumab in PPMS and I see what you are getting at.

Hate to dash your hopes. The patients randomized to placebo went into an open label extension. So they are getting the drug. So there will NOT be increased separation, because the people are being treated. But the data is exactly the same as a DMT in any progressive neuro disease, like ocrelizuamb: earlier treatment slows disease progression (the ocrelizumab OLE is strikingly similar). The patients randomized to delayed treatment will not catch up (unless there are enough drop outs, then the stats might not show the same crisp separation.

You lost me here. Perhaps you mean that neurologists who refuse to prescribe this medication despite patients desiring it while truly understanding the benefit to cost/risks ratio (cost including financial, time spent with monitoring/infusions, and potential anxiety from pt/family about ICH) fit this analogy.

I have discussed this drug seriously with perhaps 50 patients/families (perhaps 50 really good potential candidates I mean) and none of them ultimately decided to proceed. You probably have a selection bias for more highly motivated patients who want the drug more so I understand a differential in drug utilization. I am community general neurology and also neuro-op. I do genuinely wonder if you think that my lack of patients on the drug means that I am not correctly explaining the pros and cons? I won’t take it personally

With a 0 out of 50 rate, I very much doubt the patients and families understand the disease course. I've had a recent wave of people who didn't and couldn't get adu due to Medicare non-coverage despite FDA approval (cheered on by the very same bad faith people above). They are now in the moderate stages of the disease. The families now see that this disease is horrible. It is slow, but relentless, resulting in worse and worse memory, thinking, personality, function while neuropsychiatric manifestations pick up and things turn bad. And the disease is fatal over the next decade, if the family gets lucky.

Out of 50 appropriate people, and assuming they are positive for amyloid (so really out of 60-65, since our amyloid miss rate is about 15-20%), I'm going to probably treat 35-40 of them. I"d say that 5 are risk intolerant. Another 3-5 don't want medical stuff like MRIs and IVs. Another few can't deal with the diagnosis, go into denial or adopt short timelines ("I'm/they're not even that bad now"), or do Bredesen/naturopath/prayer/whatever quackery. Or I can't deal with the caregiver(s). Or a combo.

The patients who want to move forward with biomarker confirmation and treatment want to delay worsening with all their might. Those in their 50s and 60s want to see their kids have kids. Some would rather die than be a burden, so ARIA holds no fear. Some are even phobic for needles and MRIs, but are brave enough to get it done.