This observational study provides initial evidence on patient characteristics and treatment patterns that are consistent with the FDA approved prescribing information, in patients with AD who received lecanemab in real-world clinical practice, using the most recent data through October 2024. This study represents an early attempt to better understand the patient characteristics, clinical profile, and patterns of utilization of individuals receiving lecanemab in clinical practice since its approval in the United States.

Patients in our observational study were generally like those from the phase III lecanemab Clarity AD study [16], although some differences were observed. Mean age (observational study: 75.2 years; Clarity AD: 71.2 years), racial makeup—White (observational study: 77.8%; Clarity AD: 77%), use of concomitant AD medications (observational study: 47.8%; Clarity AD: 53%), and sex—female (observational study: 55.0%; Clarity AD: 52%) were generally similar between the observational and phase III study. However, fewer individuals in the observational study than Clarity AD had a diagnosis of MCI (observational study: 31.7%; Clarity AD: 62%). These results may reflect the challenges of early AD diagnosis in clinical practice [25] and are anticipated to improve based upon available treatments.

Lecanemab utilization followed FDA-approved prescribing information including dosing frequency recommendations. In our study, the average number of administrations per month was 1.9 (SD 1.0), with 16.3 (SD 11.0) days apart. These results are in line with the bi-weekly dosing frequency in the prescribing information, with a consistent median of 14 days between consecutive administrations, suggesting that neither MRI monitoring nor possible adverse events significantly interfered with lecanemab dosing. The differences in administration intervals are likely due to the occasional treatment interruptions that were observed in the study.

Most patients treated with lecanemab were adherent based on our real-world data. The use of monoclonal antibodies in clinical practice presents numerous logistical challenges for patients that include travel, cost of care, and access to healthcare resources, suggesting that longitudinal adherence to lecanemab may be more challenging outside of the Clarity AD study environment [26, 27]. Despite these challenges, we found that a minority of treated patients (17.8%) had a treatment gap or a treatment interruption (2.8%) ≥ 90 days. Patient adherence to monoclonal antibodies may continue to improve once alternative modes of drug administration become available. A monthly intravenous maintenance dosing regimen of lecanemab has recently been approved by the FDA, with reduced dosing frequency and the potential to enhance adherence and persistence [14]. Further, a subcutaneous formulation of lecanemab would allow for a quick, at-home administration, in comparison to current intravenous infusions. Subcutaneous dosing would also substantially reduce healthcare system burden, by potentially reducing healthcare facility visits, improving treatment convenience, and decreasing costs in administration.

Our data showed that most patients were diagnosed with AD rather than MCI in the real world. Possible reasons for this finding include lack of availability, adoption and access to diagnostic biomarkers, competing comorbidities in the older population, lack of clear consensus on cognitive assessments sensitive to early stages of AD, high variability of MCI symptomatology, and reimbursement issues. The underdiagnosis of MCI and dementia remains a significant issue, particularly for MCI, due to difficulties with diagnosing AD-related MCI among seniors in the general population. A recent analysis revealed 92% of potential MCI cases go undiagnosed [28]. In contrast to proactive approaches for other health conditions like anxiety disorder or colorectal screening, cognitive impairment screening has not received attention from the US Preventive Services Task Force (USPSTF) since prior to the approval of anti-amyloid monoclonal antibody treatments. With almost no screening guidance for cognitive impairment testing in the United States, standardized screening guidelines are very much needed.

General screening for cognitive impairment among seniors is a formidable undertaking since many patients would have to undergo testing after screening. Results are not always conclusive and medical agents slowing the disease process have not been available until recently. Research suggests that patients with early-stage AD who are started on monoclonal antibody treatment sooner in the disease process likely experience the greatest benefits in terms of slowing of cognitive/functional decline [29,30,31]. It is also important to emphasize that disease outcomes may also be impacted by addressing modifiable medical and lifestyle risk factors associated with dementia earlier [32]. For instance, the 2024 Lancet Commissions report on dementia prevention, intervention, and care emphasized that up to 45% of dementia cases could be prevented or delayed by addressing modifiable risk factors [33]. High LDL cholesterol represented the highest individual proportion of potentially modifiable risk at 7% whereas hypertension was 2%.

Improvements in timely diagnosis may further rely on the ability of primary care physicians to identify patients with MCI due to AD and efficiently refer them to memory specialists. In our study, most patients receiving lecanemab were treated by neurologists (82%), with <10% of patients treated by family medicine or internal medicine doctors. This likely contributed to lower recorded rates of hypertension and dyslipidemia, as these comorbidities may be under-billed by neurologists. Furthermore, we observed in our study that lecanemab users were predominantly White and urban-based, with diverse and rural-based patients relatively underrepresented. Minority populations have been shown to be less likely to receive accurate and timely diagnoses, be prescribed anti-dementia medications, and avoid hospitalization [34]. Similarly, rural residents in the US are at heightened risk for AD and face increased burdens due to health disparities [35]. Often, rural regions are ‘care deserts’ with respect to specialists—most neurologists practice in metropolitan areas but are sparsely concentrated in nonmetropolitan (5.2%) and rural (0.458%) communities [35]. These findings suggest disparities in care that deserve further research to discern the causes. Outreach programs may be warranted to close the access gap for underserved communities.

Another potential barrier to administration is access to beta-amyloid PET scans. Most beta-amyloid PET facilities are in urban areas, and there are only approximately 343 imaging facilities across the United States that offer these scans, according to the Imaging Dementia—Evidence for Amyloid Scanning Study (IDEAS) study [36]. A serum blood test for amyloid could potentially mitigate this treatment barrier, allowing for more eligible individuals to be diagnosed and for appropriate treatment to be considered at an earlier disease stage.

There are limitations to this study. Claims databases may be subject to coding errors, such as the potential miscoding of diagnoses and procedures, lack of clinical detail, and inconsistencies in billing practices [37]. Gaps in data capture may also exist as open claims data are subject to omissions of certain clinical interactions, such as MRI scans and amyloid testing. Rural/urban status based on 3-digit zip codes and Census proportions may misclassify mixed areas in our claims population. The mean follow-up duration of < 6 months in this study may also impact our abilities to investigate treatment patterns, including treatment gaps. Additionally, coverage and benefit restrictions may have impacted lecanemab utilization patterns. Finally, ICD-10-CM codes for AD do not indicate disease severity, even though the drug is indicated for treatment of individuals with early or mild stages of AD. This lack of specificity limits the ability to interpret the results based on severity of disease. These limitations notwithstanding, the results of this study provide important insights as the first real-world observations of lecanemab use in clinical practice.