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. 2023 Nov 7;101(19):e1837-e1849.
doi: 10.1212/WNL.0000000000207770. Epub 2023 Aug 16.

Eligibility for Anti-Amyloid Treatment in a Population-Based Study of Cognitive Aging

Rioghna R Pittock  1 , Jeremiah A Aakre  1 , Anna M Castillo  1 , Vijay K Ramanan  1 , Walter K Kremers  1 , Clifford R Jack Jr  1 , Prashanthi Vemuri  1 , Val J Lowe  1 , David S Knopman  1 , Ronald C Petersen  1 , Jonathan Graff-Radford  1 , Maria Vassilaki  2
Affiliations

Eligibility for Anti-Amyloid Treatment in a Population-Based Study of Cognitive Aging

Rioghna R Pittock et al. Neurology. .

Abstract

Background and objectives: Treatment options for Alzheimer disease (AD) are limited and have focused mainly on symptomatic therapy and improving quality of life. Recently, lecanemab, an anti-β-amyloid monoclonal antibody (mAb), received accelerated approval by the US Food and Drug Administration for treatment in the early stages of biomarker-confirmed symptomatic AD. An additional anti-β-amyloid mAb, aducanumab, was approved in 2021, and more will potentially become available in the near future. Research on the applicability and generalizability of the anti-β-amyloid mAb eligibility criteria on adults with biomarkers available in the general population has been lacking. The study's primary aim was to apply the clinical trial eligibility criteria for lecanemab treatment to participants with early AD of the population-based Mayo Clinic Study of Aging (MCSA) and assess the generalizability of anti-amyloid treatment. The secondary aim of this study was to apply the clinical trial eligibility criteria for aducanumab treatment in MCSA participants.

Methods: This cross-sectional study aimed to apply the clinical trial eligibility criteria for lecanemab and aducanumab treatment to participants with early AD of the population-based MCSA and assess the generalizability of anti-amyloid treatment.

Results: Two hundred thirty-seven MCSA participants (mean age [SD] 80.9 [6.3] years, 54.9% male, and 97.5% White) with mild cognitive impairment (MCI) or mild dementia and increased brain amyloid burden by PiB PET comprised the study sample. Lecanemab trial's inclusion criteria reduced the study sample to 112 (47.3% of 237) participants. The trial's exclusion criteria further narrowed the number of potentially eligible participants to 19 (overall 8% of 237). Modifying the eligibility criteria to include all participants with MCI (instead of applying additional cognitive criteria) resulted in 17.4% of participants with MCI being eligible for lecanemab treatment. One hundred four participants (43.9% of 237) fulfilled the aducanumab clinical trial's inclusion criteria. The aducanumab trial's exclusion criteria further reduced the number of available participants, narrowing those eligible to 12 (5.1% of 237). Common exclusions were related to other chronic conditions and neuroimaging findings.

Discussion: Findings estimate the limited eligibility in typical older adults with cognitive impairment for anti-β-amyloid mAbs.

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Conflict of interest statement

R.R. Pittock reports that her father has received personal compensation for serving on scientific advisory boards for F. Hoffmann-La Roche AG and his institution has received grants; his institution has received grants, personal fees, nonfinancial support, research support, and compensation for serving as a consultant for Alexion, AstraZeneca Rare Disease; he has a patent (Patent 9,891,219B2, Application 12–573942) issued and for which he has received royalties and also reports grants, personal fees, nonfinancial support, and other support from MedImmune/Horizon and has received a grant from Novelmed. J.A. Aakre and A.M. Castillo report no disclosures relevant to the manuscript. V.K. Ramanan receives research funding from the NIH and the Mangurian Foundation for Lewy Body disease research, has provided educational content for Medscape, and is an investigator in clinical trials sponsored by the Alzheimer's Association, Eisai, and the Alzheimer's Treatment and Research Institute at USC. W.K. Kremers receives research funding from NIH. C.R. Jack, Jr., has no conflicts to report. D.S. Knopman serves on a Data Safety Monitoring Board for the Dominantly Inherited Alzheimer Network Treatment Unit study. He served on a Data Safety Monitoring Board for a tau therapeutic for Biogen (until 2021) but received no personal compensation. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. He has served as a consultant for Roche, Samus Therapeutics, Magellan Health, Biovie, and Alzeca Biosciences but receives no personal compensation. He attended an Eisai advisory board meeting for lecanemab on December 2, 2022, but received no compensation. He receives funding from the NIH. P. Vemuri receives research funding from NIH. V.J. Lowe serves as a consultant for Bayer Schering Pharma, Piramal Life Sciences, Life Molecular Imaging, Eisai Inc., AVID Radiopharmaceuticals, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). R.C. Petersen serves is a consultant for Roche, Inc., Eisai, Inc., Genentech, Inc. Eli Lilly, Inc., and Nestle, Inc., served on a DSMB for Genentech, receives royalties from Oxford University Press and UpToDate, and receives NIH funding. J. Graff-Radford receives support from the NIH, is an investigator in clinical trials sponsored by Esai and the Alzheimer's Treatment and Research Institute at USC, and is a member of the Data and Safety Monitoring Board (DSMB) for StrokeNet. M. Vassilaki has consulted for F. Hoffmann-La Roche Ltd; currently she receives research funding from NIH; she has equity ownership in Abbott Laboratories, Johnson and Johnson, Medtronic, Merck, and Amgen; her spouse receives research funding from Avobis Bio, LLC. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Selection of the Study Sample
Figure 2
Figure 2. Inclusion Criteria Used in the Study for Lecanemab (A) and Aducanumab (B) Treatment
Figure 3
Figure 3. Pie Charts Represent the Participants Who Met the Inclusion Criteria for Lecanemab (A; n = 112) and Aducanumab (B; n = 104) and the Proportion of Participants Who Met None, One, or More Exclusion Criteria
See this image and copyright information in PMC

Comment in

References

    1. Cummings J, Lee G, Nahed P, et al. . Alzheimer's disease drug development pipeline: 2022. Alzheimers Dement (N Y). 2022;8(1):e12295. doi. 10.1002/trc2.12295 - DOI - PMC - PubMed
    1. Hodes RJ. NIA statement on report of lecanemab reducing cognitive decline in Alzheimer's clinical trial. Accessed January 10, 2023. nia.nih.gov/news/nia-statement-report-lecanemab-reducing-cognitive-decli...
    1. van Dyck CH, Swanson CJ, Aisen P, et al. . Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388(1):9-21. doi. 10.1056/nejmoa2212948 - DOI - PubMed
    1. Thambisetty M, Howard R. Lecanemab trial in AD brings hope but requires greater clarity. Nat Rev Neurol. 2023;19(3):132-133. doi. 10.1038/s41582-022-00768-w - DOI - PubMed
    1. Togher Z, Dolphin H, Russell C, Ryan M, Kennelly SP, O'Dowd S. Potential eligibility for Aducanumab therapy in an Irish specialist cognitive service-Utilising cerebrospinal fluid biomarkers and appropriate use criteria. Int J Geriatr Psychiatry. 2022;37(8). doi. 10.1002/gps.5789 - DOI - PMC - PubMed

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