Drug–Drug Interaction Signals Between Anti-Amyloid-β Antibodies and Antithrombotic Drugs for Amyloid-Related Imaging Abnormalities and Intracranial Hemorrhage: A FAERS Disproportionality Analysis
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Background Anti-amyloid-β (Aβ) monoclonal antibodies are disease-modifying treatments for early Alzheimer’s disease but are associated with amyloid-related imaging abnormalities (ARIA) and intracranial hemorrhage (ICH). However, the safety of concomitant antithrombotic use remains unclear. Objective To evaluate potential drug–drug interaction (DDI) signals between anti-Aβ antibodies and antithrombotic drugs for ARIA and ICH using the FDA Adverse Event Reporting System (FAERS; JAPIC AERS). Methods FAERS reports from 1997 to 2024 were analyzed. The anti-Aβ antibodies evaluated were aducanumab, lecanemab, and donanemab. Antithrombotics were aspirin, P2Y 12 inhibitors, direct oral anticoagulants, warfarin, and tissue-type plasminogen activators (tPAs). Outcomes were any ARIA, ARIA with edema or effusion (ARIA-E), ARIA with hemosiderin deposition (ARIA-H), and ICH. Individual-drug signals were assessed using reporting odds ratios and information components; DDIs were evaluated using four complementary models. Results All three antibodies showed positive signals for all outcomes. When the three antibodies were analyzed together, aspirin showed positive DDI signals for any ARIA, ARIA-E, and ARIA-H in three models. Lecanemab–aspirin also showed signals for any ARIA and ARIA-H in multiple models. For ICH, tPAs showed signals in all four models with lecanemab and in the analysis combining all anti-Aβ antibodies. Both analyses were based on the same five lecanemab reports. Conclusions DDI signals were detected for anti-Aβ antibody–aspirin combinations for ARIA and anti-Aβ antibody–tPA combinations for ICH, particularly with lecanemab. These findings may warrant careful review of aspirin indications and baseline hemorrhagic risk and caution with thrombolysis during anti-Aβ antibody treatment, although prospective validation is needed.
Source: medRxiv
Institution: Fujita Health University
Language: English
Subfield: Toxicology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7212384162