CTAD 2022 -- Endgame for AD

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J11
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Re: CTAD 2022 -- Endgame for AD

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Re: CTAD 2022 -- Endgame for AD

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With this one I would be interested in knowing what the CDR-sb was for those who received full uninterrupted dosing. Intention to treat is not the same as actually receiving the full course of treatment. However, with Lecanemab this might not cause as large a distortion as occurred with Aducanumab.
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Re: CTAD 2022 -- Endgame for AD

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Re: CTAD 2022 -- Endgame for AD

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Low symptomatic ARIA-E percents for noncarriers and heterozygotes. This isn't even with the benefit of subQ dosing.
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Re: CTAD 2022 -- Endgame for AD

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Re: CTAD 2022 -- Endgame for AD

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The primary and secondary readout has almost embarrassingly strong statistical significance. ADAS-COG14 is an objectively measured cognitive test, so the argument that the result was biased by possible patient or caregiver treatment suspicion is unsustainable.
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Re: CTAD 2022 -- Endgame for AD

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Re: CTAD 2022 -- Endgame for AD

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The one big mystery for me from the Clarity presentations was what 59.12 Centiloids should be on the SUVR scale.
The figures above seem to answer this question; The corresponding walk over from the bottom to the top gives -60 Centiloids = ~ -0.27 (calculated value from the figure is roughly -0.271 SUVR). This is somewhat surprising (if true).

The formula that seemed to work so well was:
f(X) = -5.504274 x^2 -0.240065 x - 0.007866
where x is measured in SUVR.

The SUVR --> CDR-sb conversion table for the range of predicted SUVR is given below.
For some reason the CDR-sb benefit is light by about .10 CDR-sb.

-0.26 -0.3175380224
-0.27 -0.3443100246
-0.28 -0.3721828816

-0.271 -0.34705

https://www.desmos.com/calculator/mzazbcsjbp
desmos gives the same cognitive benefit at -0.271 SUVR.
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Re: CTAD 2022 -- Endgame for AD

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Re: CTAD 2022 -- Endgame for AD

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I want to repost this one as it will be what people will tend to focus on. The red boxed numbers are the mortality patients in Clarity. The red box on the left is for the total Lecanemab treated patient group. The red box on the right is the Lecanemab treated patients who were also taking anticoagulants. Note that of the two fatalities apparently both were in the anticoagulant group. Also, these two patients were in the OLE.

Clearly, the question that springs forward for me is whether the OLE patients were somehow different from the original treatment group. For example, what was the reinclusion rules for the OLE. One could well imagine that to be included in the trial originally there would be fairly strict selection for the right patients. The patients on placebo would then have to wait for 18 months before they could receive treatment in the OLE. This isn't how typical clinical practice would work. You don't go to the doctor and then 18 months after being deemed eligible for treatment you actually receive the treatment. I wonder whether this was in any way related to the fact that both fatalities were on the OLE arm.

Above calls it as left MCA occlusion for an APOE 44 female. Treatment for this:

"In the acute setting, the interventions for an MCA stroke are IV tissue plasminogen activator (TPA) and thrombectomy, if the patient qualifies. As mentioned above, the time of onset will determine if the patient qualifies for these interventions. For IV TPA, the last known normal has to be within 4.5 hours of the administration of the thrombolytic. For thrombectomy, the last known normal has to be within 24 hours of intervention."

Have to leave this one to the experts, though thrombectomy sounds like a much better choice here than TPA.
Perhaps a black box warning to this effect should be part of the label indication for Lecanemab.
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