Abstract
BACKGROUND: All recently approved monoclonal antibodies (eg, aducanumab, lecanemab, and donanemab) for Alzheimer disease (AD) were shown to increase the risks of amyloid-related imaging abnormalities (ARIA) in randomized clinical trials, which can include brain swelling or hemorrhage. Real-world evidence (RWE) studies are critically warranted to evaluate the associated risks of ARIA and health care resource utilization (HRU) with monoclonal treatments compared with existing nonmonoclonal (eg, donepezil, memantine and rivastigmine) treatments. OBJECTIVE: To evaluate the risk of ARIA in patients receiving monoclonal vs nonmonoclonal treatments. The secondary aim was to investigate the HRUs including emergency department (ED) and inpatient visits between the 2 groups. METHODS: We conducted a retrospective study using a large electronic health record dataset. Individuals (aged ≥18 years) diagnosed with AD and receiving monoclonal treatment were matched with a nonmonoclonal treatment group using propensity score matching. An Andersen-Gill survival model was used to estimate the cumulative hazard of ARIA after adjusting for baseline comorbidities. Negative binomial regression was applied to assess the HRUs between the 2 groups. RESULTS: The monoclonal group included 240 patients. Most patients in both groups were aged 70-80 years (47.08% vs 47.29%), female (55.42% vs 56.25%), and White (85.42% vs 85.83%) in the monoclonal and the nonmonoclonal groups, respectively. The monoclonal group had significantly higher cumulative hazard of ARIA (hazard ratio = 4.65, 95% CI = 3.77-5.73; P < 0.001) compared with the nonmonoclonal group. Concurrent antithrombotic use (1.87, 1.48-2.37; P < 0.001), a history of stroke (1.59, 1.21-2.10; P < 0.001), and hyperlipidemia (1.41, 1.09-1.84; P = 0.008) were also associated with increased hazard of ARIA. Among those patients who had at least 180 days of follow-up, the monoclonal group had significantly fewer inpatient visits (β = -2.71, -3.84 to -1.58; P < 0.001) compared with the nonmonoclonal group. CONCLUSIONS: Monoclonal treatment was associated with higher cumulative hazard of ARIA but fewer inpatient visits. This study indicated the potential of RWE, despite its distinct observational design and differences from randomized clinical trials, to serve as a credible proof-of-concept in postapproval assessment and to inform personalized treatment guidelines based on patients' risk factors.