Drug-Drug Interaction Signals Between Anti-Amyloid-β Antibodies and Antithrombotic Drugs for Amyloid-Related Imaging Abnormalities and Intracranial Hemorrhage: A FAERS Disproportionality Analysis

Background: Anti-amyloid-{beta} (A{beta}) 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-A{beta} 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-A{beta} antibodies evaluated were aducanumab, lecanemab, and donanemab. Antithrombotics were aspirin, P2Y12 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-A{beta} antibodies. Both analyses were based on the same five lecanemab reports. Conclusions: DDI signals were detected for anti-A{beta} antibody-aspirin combinations for ARIA and anti-A{beta} 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-A{beta} antibody treatment, although prospective validation is needed.