Adverse Events Associated With Recently Approved Alzheimer's Drugs: A Real-World Pharmacovigilance Study
Author(s)
Dhanish Revanth Rangaswamy Nandakumar, MPH, Sahil Bhave, MS, Ambarish J. Ambegaonkar, PhD;
Apperture LLC, Marlboro, NJ, USA
Apperture LLC, Marlboro, NJ, USA
OBJECTIVES: Alzheimer's disease (AD) affects approximately 58 million Americans above age 65 and currently has two therapeutic approaches: symptom-reducing and slowing disease-progression. Aducanumab, lecanemab, and donanemab were recently approved therapies targeting beta-amyloid removal in the brain. Given limited real-world safety data, this study aims to analyze adverse events associated with these drugs using the FDA Adverse Event Reporting System (FAERS) database.
METHODS: FAERS data from Q1 of 2023 to Q3 of 2024 was utilized with lecanemab and aducanumab as the drugs of interest. Adverse events were coded using MedDRA terminology, with preferred terms mapped to System Organ Classes (SOCs). Descriptive statistics were generated for patient demographics, reporter characteristics, and outcomes. Safety signals were identified through disproportionality analysis using Reporting Odds Ratios (ROR) with 95% confidence intervals. Sensitivity analysis was conducted for aducanumab related adverse events from prior years.
RESULTS: Adverse event cases were reported for lecanemab (n=1336) and aducanumab (n=250) in patients aged 65 years or older (55.6 and 67.2%). Events were reported by patients (42.8 and 46.6%) and physicians (29.6 and 38.8%) with over 98% reporting these drugs as primary suspect. Nervous system disorders were the predominant SOC for both drugs (aducanumab 75.4%, lecanemab 58.6%). For aducanumab, amyloid-related imaging abnormalities (ARIA)-related events dominated, with ARIA-edema (ROR=8,884.02, 95%CI: 6,544.9-12,098.7) and ARIA-microhemorrhages (ROR=6,132.17, 95%CI: 4,386.14-8,600.23) comprising 58.5% of events. Lecanemab showed a broader range of adverse events, with headache most frequent (20%, ROR=8.43, 95%CI: 7.37-9.66), followed by ARIA events (21.3% combined), chills (10.5%, ROR=20.99, 95%CI: 17.59-25.07), and fatigue (9.6%, ROR=2.37, 95%CI: 1.97-2.85). Comparisons to AEs in label demonstrated that for aducanumab, cerebral hemorrhage was not previously reported.
CONCLUSIONS: FDAERs provide a rapid understanding of Real-world safety signals for AD therapies which demonstrated similar overall organ-level adverse effects, however distinct differences in specific events were noted.
METHODS: FAERS data from Q1 of 2023 to Q3 of 2024 was utilized with lecanemab and aducanumab as the drugs of interest. Adverse events were coded using MedDRA terminology, with preferred terms mapped to System Organ Classes (SOCs). Descriptive statistics were generated for patient demographics, reporter characteristics, and outcomes. Safety signals were identified through disproportionality analysis using Reporting Odds Ratios (ROR) with 95% confidence intervals. Sensitivity analysis was conducted for aducanumab related adverse events from prior years.
RESULTS: Adverse event cases were reported for lecanemab (n=1336) and aducanumab (n=250) in patients aged 65 years or older (55.6 and 67.2%). Events were reported by patients (42.8 and 46.6%) and physicians (29.6 and 38.8%) with over 98% reporting these drugs as primary suspect. Nervous system disorders were the predominant SOC for both drugs (aducanumab 75.4%, lecanemab 58.6%). For aducanumab, amyloid-related imaging abnormalities (ARIA)-related events dominated, with ARIA-edema (ROR=8,884.02, 95%CI: 6,544.9-12,098.7) and ARIA-microhemorrhages (ROR=6,132.17, 95%CI: 4,386.14-8,600.23) comprising 58.5% of events. Lecanemab showed a broader range of adverse events, with headache most frequent (20%, ROR=8.43, 95%CI: 7.37-9.66), followed by ARIA events (21.3% combined), chills (10.5%, ROR=20.99, 95%CI: 17.59-25.07), and fatigue (9.6%, ROR=2.37, 95%CI: 1.97-2.85). Comparisons to AEs in label demonstrated that for aducanumab, cerebral hemorrhage was not previously reported.
CONCLUSIONS: FDAERs provide a rapid understanding of Real-world safety signals for AD therapies which demonstrated similar overall organ-level adverse effects, however distinct differences in specific events were noted.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
EPH11
Topic
Epidemiology & Public Health
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
SDC: Neurological Disorders