arsenal09490 t1_iybcye3 wrote on November 30, 2022 at 3:15 AM

The full trial can be found in today's issue of NEJM: van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer’s Disease. NEJM. 2022;387(22):E-pub ahead of print. DOI: 10.1056/NEJMoa2212948

Overall, this does appear to be a promising treatment. Upon reading the study, my biggest criticism is that the primary endpoint is not a tool validated for measuring Alzheimer's progression. CDR-SB is mainly used for initial staging and diagnosis. However, the secondary endpoints that better assess progression were also significant, which does point toward an efficacious medication.

Relevant_synapse OP t1_iybev6a wrote on November 30, 2022 at 3:30 AM

What do you think about the rates of ARIA and the potential interaction with anticoagulants?

arsenal09490 t1_iyboubb wrote on November 30, 2022 at 4:58 AM

The rates of ARIA were concerning, but they were pretty localized in patients with ApoE ε4 carrier. Still high in non-carriers, but at least that has a better risk-benefit profile. Additionally, only 0.8% of ARIA cases were considered severe. That being said, the risk of ARIA leading to discontinuation will make it difficult to identify ideal candidates until more data comes out.

I do not think lecanemab should interfere with any DOACs or antiplatelets? However, patients on these medications may be at an increased risk of ARIA and/or brain bleeds (especially if the have a stroke and need tPA). So the potential additive blood thinning effect may further limit the population this drug could be used in.

Relevant_synapse OP t1_iybp4zt wrote on November 30, 2022 at 5:01 AM

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

arsenal09490 t1_iybpqh3 wrote on November 30, 2022 at 5:07 AM

No, I have not had a chance to look at those reports yet. Are they published or just announced in the press release?

Relevant_synapse OP t1_iybq2ec wrote on November 30, 2022 at 5:10 AM

Not sure about the first case. Per this article in Science Insider, the second case has at least been written up?

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

Kooky_Edge5717 t1_iycfqht wrote on November 30, 2022 at 10:49 AM

I’m not familiar with the various tools/scores, and I won’t be able to check the full paper for a while. Do you happen to know the minimum clinically important difference in any of the scores?

Relevant_synapse OP t1_iycgkru wrote on November 30, 2022 at 11:00 AM

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