This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Background and Objectives To assess the incidence of amyloid-related imaging abnormalities (ARIA) in clinical trials of anti–β-amyloid (Aβ) immunotherapy and compare the incidence among different agents and clinical characteristics to identify possible predisposing factors for ARIA.
Methods The PubMed and Embase databases were searched for clinical trials of anti-Aβ immunotherapy published on or before January 12, 2022. Phase 2 or 3 randomized controlled trials reporting detailed data sufficient to assess the incidence of ARIA were selected. The pooled incidences of ARIA and subgroup analyses according to agent and ApoE-4 carrier status were calculated using the DerSimonian-Liard random-effects model. The proportion of symptomatic ARIA cases was also calculated.
Results In total, 19 eligible studies, including 24 cohorts, were identified and 9,429 patients were analyzed. The overall pooled incidence of ARIA-effusion (E) and ARIA-hemorrhage (H) was 6.5% and 7.8%, respectively. In the subgroup analysis, the incidence of ARIA was different according to the anti-Aβ immunotherapy agent. The cohorts treated with aducanumab had a significantly higher incidence of ARIA-E and ARIA-H (30.7% and 30.0%, respectively; both p < 0.001) compared with cohorts from other drugs. In subgroup analysis according to ApoE-4 carrier status, the incidences of ARIA-E and ARIA-H were higher in the ApoE-4 carrier group than those in the ApoE-4 noncarrier group, but there was no statistical significance (ApoE-4 carrier vs noncarrier, ARIA-E: 8.6% vs 6.9%, p = 0.663, and ARIA-H: 10.5% vs 6.6%, p = 0.398). The pooled proportion of asymptomatic ARIA, detected by routine scheduled MRI surveillances, was 80.4%.
Discussion The overall incidences of ARIA-E and ARIA-H were 6.5% and 7.8%, respectively, and the pooled proportion of asymptomatic ARIA was 80.4%. The cohorts treated with aducanumab showed a significantly higher incidence of ARIA-E and ARIA-H (30.7% and 30.0%) compared with other drugs.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ARIA=
- amyloid-related imaging abnormalities;
- ARIA-E=
- ARIA-effusion;
- ARIA-H=
- ARIA-hemorrhage;
- FDA=
- Food and Drug Administration
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editors were Brad Worrall, MD, MSc, FAAN and Rawan Tarawneh, MD.
CME Course: NPub.org/cmelist
- Received October 12, 2021.
- Accepted in final form June 1, 2022.
- © 2022 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
- Reader Response: Incidence of Amyloid-Related Imaging Abnormalities in Patients With Alzheimer Disease Treated With Anti-β-Amyloid Immunotherapy: A Meta-analysis
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
More Online
Differences in Age-related Retinal and Cortical Atrophy Rates in Multiple Sclerosis
Prof. Massimo Filippi and Dr. Paolo Preziosa